Device to detect and treat apneas and hypopnea

ABSTRACT

A method and apparatus for the treatment of Sleep Apnea events and Hypopnea episodes wherein one embodiment comprises a wearable, belt like apparatus containing a microphone and a plethysmograph. The microphone and plethysmograph generate signals that are representative of physiological aspects of respiration, and the signals are transferred to an imbedded computer. The embedded computer extracts the sound of breathing and the sound of the heart beat by Digital Signal Processing techniques. The embedded computer has elements for determining when respiration parameters falls out of defined boundaries for said respiration parameters. This exemplary method provides real-time detection of the onset of a Sleep Apnea event or Hypopnea episode and supplies stimulation signals upon the determination of a Sleep Apnea event or Hypopnea episode to initiate an inhalation. In one embodiment, the stimulus is applied to the patient by a cutaneous rumble effects actuator and/or audio effects broadcasting.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Continuation to U.S. patent application Ser. No.15/963,709 filed Apr. 26, 2018, which is a Continuation of U.S. patentapplication Ser. No. 12/277,386 filed Nov. 25, 2008 which claims thebenefit of U.S. Provisional Application No. 60/990,035, filed Nov. 26,2007, each of which are incorporated herein by reference in theirentireties.

TECHNICAL FIELD

The present invention relates to an apparatus to detect and endoccurrences of Sleep Apnea event and Hypopnea episode, in a manner thatwill decrease or eliminate hypoxia, hypercapnia and the disturbance ofpulmonary hemodynamics.

BACKGROUND

Sleep disordered breathing (SDB) is a group of breathing disorders thatoccur during periods of sleep. The most serious forms of sleepdisordered breathing involve an intermittent cessation (apnea) orreduction (hypopnea) of ventilation during sleep that results inphysiologic disturbances including a decrease in blood oxygen levels(hypoxia), increase in CO2 (hypercapnia), and autonomic activationresulting in vasoconstriction. The long term effects of thesephysiological changes are associated with the development of cardiacarrhythmias, congestive heart failure, cardiac ischemia, hypertension,heart disease, brain damage, and diabetes. Another form of sleepdisordered breathing is respiratory effort-related arousals (RERA)defined as “obstructed events that do not meet the criteria for apnea orhypopnea but that nevertheless cause an arousal. More specifically, RERAare defined as the absence of apnea/hypopnea but with progressivenegative Pes (esophageal pressure) lasting about 10 seconds culminatingin an arousal.” (Halasz et al, 2004)

The causes of the various forms of sleep apnea and hypopnea are notfully understood.

There are three general types of sleep apnea: obstructive sleep apnea(OSA), central sleep apnea (CSA), and mixed sleep apnea. Obstructivesleep apnea (the most common type) is characterized by a blockage orocclusion of the oropharyngeal (upper) airway due to a loss of patencyof its muscles. With obstructive sleep apnea, respiratory effortcontinues and may be apparent as paradoxical movement of the thorax orabdomen. This paradoxical movement acts as a one way piston: air leavesthe lungs but little or none can enter. The cause or causes ofObstructive Sleep Apneas is still a matter of much debate and research.

The average Apnea event lasts 20 seconds, however events of 2 to 3minutes are not unknown. During the event, a number of physiologicalevents occur. These include a vagal bradycardia, an increase in bloodpressure, an increase in norepinephrine, and paradoxical respiratoryefforts with increased respiratory effort. As an apnea event progresses,there is an increasing effort to breathe, increasing carbon dioxide(hypercapnia), decreasing oxygen, and increasing level ofproprioception. The longer the Apnea event, the more extreme thesechanges are.

At the end of an Apnea event tone returns to the upper airway muscles sothat the upper airway suddenly re-opens (restoration of patency). Thiscan be associated with a sudden gasp or choking as air rapidly entersthe lungs, and with surges in heart rate and blood pressure.

It has been believed that an arousal from a deeper stage of sleep to alighter stage of sleep was required to terminate an Apnea episode;however studies have cast doubt on that assertion. “[During sleep] thebrain is permanently active and is able to control the autonomic,metabolic and hormonal changes that take place within the body andsimultaneously determine the behavioral responses to the externalstimuli. Although sleep is characterized by decreased consciousperception, these tasks are accomplished nevertheless during sleepthrough a gradual activation of the brain or through a partialactivation confined to some cerebral areas (Ujszaszi and Halasz 1988) .. . . In this way, the sleeping brain not only regulates the reactionsbut also assimilates in its functions the incoming information. From afunctional point of view, sleep modulates and is modulated by thisseries of interactions.” (Halasz et al, 2004)

“Compared with wakefulness, sleep is subjectively perceived as a reducedresponsiveness to environmental stimuli induced by a selective closureto the inputs arriving from the external world (Steriade 2000a). Thefilter that gates the flux of information from the peripheral receptorsto the cortex is situated in the thalamocortical connections where theincoming signals are blocked or attenuated via synaptic inhibition. Thismechanism modulates the susceptibility of the cerebral cortex to all theactivating stimuli. In particular, the generators of cortical electricalactivity are modified during sleep and shift from the production of lowamplitude high-frequency electroencephalographic (EEG) activity (LAHFmode) typical expression of the massive activation of the corticalcells, to the production of high amplitude low-frequency EEG activity(HALF mode) indicating a widespread synchronization of the corticalcells (Steriade and Llinas 1988; Steriade and McCarley 1990; Steriade etal. 1990). Rapid eye movement (REM) sleep, which appears later in thenight, is characterized by the simultaneous occurrence of LAHF EEGactivity, absence of muscle tone and recurrent rapid eye movements . . ..

Attention to the functions and importance of activated brain states wasfirst raised by Moruzzi and Magoun (1949) who demonstrated an‘activation’ process in the changes of EEG waves and verified theirbrainstem origin. The discovery and localization of brainstem reticulararousal system (RAS) was made by lesion experiments and by electricalstimulation of the brainstem reticular core (Hobson 1978). The EEGeffect of arousal was called as ‘desynchronization’, but the coincidenceof desynchronization with the concept of arousal has created severelimitations to the future development of the field. Although slowsynchronization thalamic devices are really decoupled and the EEGactivity is flattened, a fast (30-40 Hz) EEG pattern synchronizationappears in the cortical and thalamic networks (Steriade 1995).Accordingly, the term ‘desynchronization’ should be considered as arapid shift from HALF, typical of sleep, to LAHF, typical ofwakefulness.” (Halasz et al, 2004)

“The concept of ‘arousal’ has a long history, which is closely connectedwith the development of concepts about the neurophysiology of sleep andwakefulness. The criteria and measure of ‘arousal’ are controversialissues; hence, ‘arousal’ has several definitions (Halasz et al. 1979;Lofaso et al. 1998; Martin et al. 1997a; Rees et al. 1995; Schieber etal. 1971; Terzano et al. 1985) and several EEG, behavioral and autonomicaspects.” (Halasz et al, 2004)

An “EEG arousal,” “cortical arousal,” or “ASDA arousal” is defined asfollows: “The American Sleep Disorders Association (ASDA) produced aconsensus report (Atlas Task Force 1992) on the criteria of arousals insleep in the early 1990s. [ASDA] arousal is defined as a rapidmodification in [delta] EEG frequency, which can include theta and alphaactivity, and/or frequencies higher than 16 Hz but not spindles. It canbe accompanied by an increase of electromyographic activity, of cardiacfrequency or by body movements. An [ASDA] arousal must be preceded by atleast 10 s of continuous sleep [and must last at least 3 seconds] . . .. The conventional [ASDA] definition of arousal includes a cluster ofphysiologic manifestations expressed by an activation ofelectrocorticographic rhythms, an increase of blood pressure and muscletone and a variation of heart rate . . . [ASDA] arousal, by definition,means cortical activation.” (Halasz et al, 2004)

Changes in rhythm observed on EEG do not necessarily representconventional cortical [ASDA] arousals. “Micro-Arousals (MA),” also knownas “Transient activations” or “phases d'activation transitoire” (PAT)were originally defined as brief “phasic EEG events which were notassociated with awakenings regardless of their desynchronizational orsynchronizational (sleep response-like) morphology and regardless oftheir connection with autonomic or some sort of behavioral arousal . . .. The criteria for MA in NREM sleep given by Schieber et al. (1971) werethe following: increase in EEG frequencies in conjunction with decreaseof amplitudes, disappearance of delta waves and spindles, transitoryenhancement of muscle tone or phasic appearance of groups of musclepotentials, movements of the limbs or changes in body posture,transitory rise in heart rate. In REM sleep the criteria for MAs weretemporary disappearance of eye movements and appearance of alphaactivities. The duration of these changes varied from some seconds tomore than 10 s. Temporary activation is followed by deactivation leadingto a bi-phasic character of the phenomenon.” (Halasz et al 2004) UnderASDA criteria (mASDA), transient increases in frequency lasting lessthan 3 seconds are classified as microarousals rather than corticalarousals.

Many other types of ‘arousals’ have been defined in the sleepliterature. “Any behavioral expression, which occurs associated withlow-voltage fast-EEG activities, is classified as a ‘behavioral arousal’(Moruzzi and Magoun 1949). Similar features are shown by ‘movementarousals’ described as any increase in electromyographic activity thatis accompanied by a change in any other EEG channel (Rechtschaffen andKales 1968). When the EEG compartment is involved by transientdesynchronization patterns [as specified in the ASDA criteria],regardless of the participation of the autonomic system or behavioralcomponents, it was held as ‘cortical arousal’ (Atlas Task Force 1992).When there is evidence of vegetative or behavioral activation associatedwith an EEG pattern different from conventional [ASDA] arousal the eventwas defined as ‘subcortical arousal’ (McNamara et al. 2002; Rees et al.1995). When an autonomic activation appears isolated or in conjunctionwith a respiratory event, but without any concomitant EEG sign, it iscommonly defined as an ‘autonomic arousal’ (Martin et al. 1997b; Pitsonand Stradling 1998). There is an autonomic ‘overarousal’ compared withthe periods of arousal from continuous awake state during periods ofawakening from NREM sleep (Homer et al. 1997), that also represents acertain kind of quantitative decoupling between the autonomic and othercomponents of arousal.” (Halasz et al 2004)

The term “subcortical arousal” therefore does not imply that no areas ofthe cerebral cortex are active, but rather means an activation eventduring which the observed EEG pattern differs from the ASDA-specifiedpattern that defines a ‘cortical arousal’ (‘EEG arousal’). By definitiona ‘subcortical arousal’ is not associated with a change of ASDA sleepstage classification, else it would meet the ASDA criteria for a‘cortical arousal’. Although they may not be classified as ‘EEGarousals’ (cortical arousals), movement and behavioral arousals alwaysinvolve some degree of EEG or autonomic activation: “movement andbehavioral arousals without either EEG or autonomic concomitants do notexist.” (Halasz et al, 2004)

A particular EEG ‘cyclic alternating pattern’ (CAP) is “recognized as aphysiologic component of normal NREM sleep (Bruni et al. 2002; Lofaso etal. 1998; Parrino et al. 1998; Terzano and Parrino 2000)” and defined as“different EEG features endowed with activating properties and coalescedinto a common ‘brain beat’ (Terzano et al. 1985). In the CAP framework,‘arousals’ are viewed as complex phenomena involving not only corticalareas but also other brain centers and peripheral neural components.These components are involved with different latencies and intensitiesbut are nevertheless transformed into a unitary phenomenon by thereciprocal interneural connections (Moruzzi 1972). The activatingphenomena occurring within the somato-vegetative systems do not alwayscorrespond to a cortical activation.” (Halasz et al, 2004) The cyclicalternation of CAP is divided in two major phases. “The CAP A-phasebehaves like the synchronization arousals, can be elicited by sensorystimuli and is associated with clearly detectable autonomic discharges.Later the Parma school differentiated within the CAP A-phase threesubtypes. In subtype A1, EEG synchrony is the predominant activity. Ifpresent, EEG desynchrony occupies less than 20% of the entire phase Aduration. Subtype A1 is generally associated with mild autonomic andmuscle activity. Subtype A2 contains a mixture of slow and rapid rhythmswith 20-50% of phase A occupied by EEG desynchrony. Subtype A2 is linkedwith a moderate increase of muscle tone and/or cardiorespiratory rate.In subtype A3, the EEG activity is predominantly fast low voltagerhythms with greater than 50% of phase A occupied by EEG desynchrony.Subtype A3 is coupled with a remarkable activation of muscle tone and/orautonomic activities (Terzano et al. 2001).” In contrast, “phase B ofCAP is closely related to the repetitive respiratory events ofsleep-disordered breathing (Parrino et al. 2000a; Terzano et al. 1996;Thomas 2002), and only the powerful autonomic activation during thefollowing CAP-A phase can restore post apnea breathing (Parrino et al.2000b; Terzano et al. 1996) . . . . During sleep, an acoustic stimulusdelivered during stable non-CAP can evoke a prolonged CAP sequence(Terzano and Parrino 1991).” (Halasz et al, 2004)

Arousals of all types may arise spontaneously: “Spontaneous arousals arenatural guests of the sleeping brain (Boselli et al. 1998) and appearregularly embedded within the CAP process (Parrino et al. 2001; Terzanoet al. 2002). However, arousal phenomena are also known to occur inresponse to sleep-disturbing factors. Increased amounts of arousals area regular finding of obstructive sleep apnea syndrome (OSAS), buttypical manifestations of secondary cortical events are also the‘respiratory effort-related arousals’ (RERA) known as obstructed eventsthat do not meet the criteria for apnea or hypopnea but thatnevertheless cause an arousal. More specifically, RERA are defined asthe absence of apnea/hypopnea but with progressive negative esophagealpressure lasting approximately 10 s culminating in an arousal. RERA areincreased both in OSAS and in the ‘upper airway resistance syndrome’(UARS) as a reaction of the sleeping brain to a repetitive breathingdisturbance. RERA are secondary to subtle obstructions of the upperairway during sleep and can appear in the absence of apneas andhypopneas, causing excessive daytime sleepiness. The common abundance ofRERA in sleep-disordered breathing (SDB) has supported the idea thatarousals are a sign of disturbed sleep and that arousal responsesreflect abnormal breathing (Douglas 2000).” (Halasz et al 2004)

Cortical (ASDA, EEG) arousal is not necessary for termination ofobstructive apnea or upper airway resistance syndrome events. “Someobstructive events terminate without obvious cortical [ASDA] arousal.”(Halasz et al 2004)

“Black et al. (2000) and Poyares et al. (2002) have found that airwayopening may occur in UARS subjects with a predominant increase [ratherthan a decrease] in delta power. In other words, reopening of the airwayat wakefulness and disappearance of abnormal UARS are not necessarilyassociated with an [ASDA] arousal. Reopening of a the airway with an EEGpattern of delta has been also observed in OSAS patients (Berry et al.1998). Involvement of either slow or fast EEG responses depends on theregulation of upper airway pathway. Respiratory patterns that needcorrection activate the CNS. This activation varies, depending on thesensory recruitment and the adequacy of the response. A respiratorychallenge can be resolved by CNS activation without involving a cortical[ASDA] arousal.”

“In the vast majority of patients, if not in all patients, [ASDA]arousal is required neither to initiate UA (Upper Airway) opening nor toobtain adequate flow. UA opening would occur at approximately the sametime regardless of when or whether arousal occurs and the flow responsein most patients would still be timely and adequate. Arousals areincidental events that occur when the thresholds for arousal andarousal-independent opening are close to each other, as they appear tobe in patients with OSA. By promoting an unnecessarily high flowresponse at UA opening, arousals help perpetuate cycling and likelyexacerbate OSA.” (YOUNES, Magdy. Role of Arousals in the Pathogenesis ofObstructive Sleep Apnea. American Journal of Respiratory and CriticalCare Medicine: Mar. 1, 2004, which is hereby incorporated by reference).

“Definition of Arousals and their Onset (T/AROUSAL). A more detailedaccount of Definition of Arousals and their Onset (T/AROUSAL) is givenin the online supplement. A combination of EEG inspection and Fourieranalysis was used. First, three EEG leads were inspected for ahigh-frequency shift greater than 3 seconds. If so, T/AROUSAL was theearliest point where the change occurred in any lead. A central EEG leadwas analyzed by discrete Fourier transform in 3-second, nonoverlappingepochs spanning baseline (20 epochs) and dial-down. EEG power in thedelta, theta, alpha, sigma, and beta ranges was computed. Confidenceinterval of 95% in baseline epochs was calculated for each frequencyband. An arousal was deemed present at Tflow if a visible arousal thatmeets conventional criteria (Arousals EEG. Scoring rules and examples: apreliminary report from the sleep disorders atlas task force of theAmerican sleep disorders association. Sleep 1992; 15:174-184) waspresent or if total high-frequency power (7.3-35.0 Hz) in the Tflowepoch was greater than the upper bound of the 95% confidence interval .. . .

Several previous reports noted the occurrence of UA opening withoutovert arousal (2-8). A number of explanations were proposed that wouldstill be consistent with arousal-mediated opening (see Berry andcoworkers [4] for review). What follows is a discussion of thesepossibilities and how they were addressed in this study.

1. An increase in EEG high frequency may be present but is equivocal orit lasts less than 3 seconds. This was addressed by comparing EEG powerspectrum at UA opening with 20 baseline epochs. Arousal was called whenhigh frequency content was significantly higher than baseline even ifthe change did not meet conventional criteria. This analysis woulddetect arousals even if the increase in high frequency involved afraction of the epoch, so long as the change is outside the rangeobserved in baseline.

2. Arousal may take the form of an increase in slow wave activity. Someinvestigators noted an increase in delta power near the end ofobstructive events (8, 38). The significance of this phenomenon isunknown. Some believe it is an early or mild form of arousal (see Sforzaand coworkers [39] for a review). Others believe it representsaccelerated progression to deep sleep in sleep-deprived patients (38).An increase in delta was found in 30% of observations classified as type1 or 2 (see Table E1 in the online supplement). There was, however, nodifference in flow response whether such changes were present or not(see Figure E7A in the online supplement). Thus, even if delta increasesare considered as arousals, they cannot be responsible for UA opening.

3. Arousals may be present without any cortical changes (subcortical orautonomic arousals). This possibility was excluded by demonstrating thatheart rate was not higher at UA opening (in fact it was lower) than inthe preceding breaths. The evidence for subcortical arousals stems fromobservations that external stimuli (e.g., acoustic) can increase heartrate and blood pressure even without cortical arousals (40, 41).Although heart rate and blood pressure responses to external stimuli mayvary in individual subjects, the average responses invariably involve anincrease in both variables (41-44). Thus, lack of an average increase inheart rate at UA opening in types 1 and 2 effectively rules outautonomic arousals at UA opening (an increase in blood pressure maystill occur at UA opening, however, because of the increase inintrathoracic pressure [decreased cardiac afterload] and reduction inpulmonary vascular resistance as a result of improvement in alveolar gastensions). Because respiratory muscle responses with subcorticalarousals are considerably less than the autonomic response (compareventilatory response to subcortical arousal in Badr and coworkers [45]with autonomic response in the same subjects in Morgan and coworkers[41]), lack of an autonomic response makes it extremely unlikely that UAopening in these cases was produced by subcortical arousals. Twoobservations from this study further support this conclusion:

First, flow response in Breath 1 was similar whether cortical arousalwas imminent (arousal in Breath 2) or not (FIG. 7 ). To the extent thatactivity in subcortical mechanisms must have been higher when arousalwas imminent, this lack of difference suggests that subcortical arousalmechanisms do not exert an important effect on UA dilators. Second, flowresponse in types 1 and 2 was, on average, 52% of the response in type 3(data from FIG. 6 ). It is difficult to explain this magnitude byarousals that could not be seen, could not be detected by Fourieranalysis, and that were not strong enough to mount a pressor response.Basner and coworkers (46) found that acoustic stimuli applied duringspontaneous obstructive apneas decreased their duration by 2 secondswhen no overt (greater than 3 seconds) cortical arousal resulted. Thiswas only 20% of the reduction produced by stimuli with overt arousal.This value of 2 seconds overestimates the potency of subcorticalarousals; in most cases classified as “no arousal,” there were corticalchanges that did not meet standard criteria (see discussion in Basnerand coworkers [46]). Thus, the potency, if any, of subcorticalmechanisms in opening UA is miniscule.

4. Cortical arousals may be present in unmonitored areas. See onlinesupplement.

5. In a minority of type 1 and 2 observations, there were changes in oneor more high-frequency bands, but they were not sufficient to increasetotal high-frequency power above baseline (see Table E1 in onlinesupplement). These are almost certainly analytical or technicalartifacts (see online supplement). Furthermore, neither flow response(see Figure E7A in the online supplement) nor heart rate response (seeFigure E9 in the online supplement) was different in these cases fromresponses where there were no EEG changes at all.” (Younes 2004)

“Evidence for Nonessentiality of Arousal. This study produced muchevidence that arousal is not essential for UA opening:

1. The relation between Tflow and Tarousal was quite inconsistent (FIG.3 ). If arousal causes opening, why does it occur sometimes before andsometimes after opening, even in the same patient? Most patients (78%)displayed different types at different times and, even within the sameresponse type in the same patient, the difference between Tflow andTarousal varied considerably (see Figure E6 in the online supplement).This strongly suggests that the association is incidental.

2. Type 3 was much less frequent when obstruction was milder (FIG. 4A).If arousal is required for UA opening with a severe hypopnea, why is itnot required with a milder one? That UA opening can occur withoutarousal at any obstruction severity indicates that the relation betweenUA dilators' activation and opposing forces is such that the dilatorsprevail, in due course, without arousal. If so, it is difficult toenvision a scenario whereby UA dilators can prevail without arousal atone level of severity but not at a higher one (FIG. 9 ).

3. Frequency of UA opening without arousal increased with delta power(FIG. 4B). Why should arousal be needed in light but not deep sleep?Obstruction was no less severe. Latency to UA opening was also notaffected by delta power. Thus, dynamics of compensatory responses werenot different. Arousal threshold increases with delta power (10-12). Themost reasonable interpretation is that arousal-independent compensatorymechanisms are capable of opening the UA, but when arousal threshold islow, arousal occurs first or concurrently.

4. Dingli and coworkers (7) and Rees and coworkers (2) reported thatduration of spontaneously occurring apneas-hypopneas was not differentwhether or not an arousal occurred (i.e., type 1 vs. types 2 and 3).Perhaps, it may be argued, that in a minority of events (i.e., type 1)arousal-free compensation is possible but in the majority (types 2 and3) arousal is needed. However, in this study latency to opening was thesame whether arousal occurred before (type 3) or after (type 2) opening(FIG. 5 ). What was different was latency to arousal (FIG. 5 ). Theinescapable conclusion is that arousal is irrelevant to when UA openingoccurs.

It follows that if a patient opens UA without arousal even once, he/shewill have demonstrated an ability to open without arousal under otherconditions if arousal does not occur first. That 78% of patientsdeveloped type 1 or type 2 response in at least one dial-down (seeFigure E6 in the online supplement) implies that the great majority donot need arousal to open the UA.

Only 18 patients (22%) had exclusively type 3 responses. Ten of these,however, developed lengthy periods of stable breathing (greater than 50%of sleep time) during polysomnography in body positions where dial-downsshowed complete obstructions (n=8) or moderate hypopneas (n=2). This isunequivocal evidence that a patient can mount effective compensationwithout arousal. Thus, only eight patients (10%) failed to open the UAwithout arousal at any time. It is possible that a small minority needsarousal. It is, however, also possible that in such patients arousalthreshold was consistently low or that the mechanical abnormalities weresufficiently severe that it was difficult to mount the necessary dilatorrecruitment without reaching arousal threshold first.

In summary, the present findings indicate that in the vast majority, ifnot in all, of the patients, arousal is not required for UA opening.”(Younes 2004)

“The conceptual basis of the ASDA criteria is that arousal [as definedby ASDA criteria] is a marker of sleep disruption, a detrimental andharmful thing.” (Halasz et al, 2004) Although cortical activation is thegold standard for definition of ‘arousal,’ several studies show thereare different levels of central nervous system activation. At the lowerrange of ‘subcortical arousal’ responses are those inducing reflex motorresponses, autonomic activation, and appearance of slow wave EEGactivity such as delta bursts (D-bursts) and K-complex bursts (Kbursts),none of which meet the ASDA definition for cortical arousals andtherefore fall into the category of ‘subcortical arousals.’ At the upperrange are arousal responses implying a cortical activation representedby microarousals (MA) and phases of transitory activation (PAT), whichmay include high frequency content but nonetheless do not meet the ASDAdefinition for cortical (EEG) arousals and therefore fall into thecategory of ‘subcortical arousals.’

External stimuli may induce significant autonomic and somatic responseswithout causing an ASDA ‘cortical arousal’: “Somatosensory and auditorystimulation during sleep may result in cardiac, respiratory and somaticmodifications without overt EEG activation (Carley et al. 1997;Winkelman 1999).” (Halasz et al, 2004)

“The EEG . . . must be recorded unambiguously to differentiate betweensleep and wakefulness. Briefly, in humans a sleep stage I ischaracterized by a modified alpha rhythm and low amplitude EEG; stage 2shows the typical spindles (14 Hz) and stages 3 and 4 show an increasingamount of slow waves (1-4 Hz).” (Velluti, 1997)

“Interactions between sleep and sensory physiology have been described,an important one being that any sensory stimulation, if strong enough,will always awaken the sleeping subject regardless of the sleep stage.All sensory systems reviewed demonstrated some influence on sleep and,at the same time, the sensory systems undergo changes that depend on thesleeping or awake state of the brain. Interestingly enough, everysensory system shows an efferent pathway, i.e. centrifugal fibres thatreach practically all nuclei of the afferent pathway as well as thereceptors themselves. Thus, sensory information entering through thereceptors may alter sleep and waking physiology and, conversely, thesleeping brain imposes rules on incoming information.” (Velluti, 1997)

“As the only sensory system remaining [fully] active while asleep (atleast in a microosmatic animal) a special relationship may be consideredto exist between the auditory system and sleep. It seems to act as aconstant guardian to signal danger, a predator or perhaps also prey. Asecond characteristic that makes the auditory system unique is itsconspicuous efferent component, featuring a complex anatomy located inparallel to the classic ascending pathway (Rassmusen 1946; Desmedt 1975;Saldana et al. 1996), and functioning as an input controllerparticularly through the action of its most peripheral stages, theolivo-cochlear system (Galambos 1956; Fex 1962; Guinan 1986; Velluti andPedemonte 1986; Velluti et al. 1989).” (Velluti, 1997)

“Upon sensory stimulation, a special evoked EEG pattern is described(Loomis et al. 1938) designated as the K-complex. Appearing in responseto sensory stimulation, as well as spontaneously, K-complexes areobserved in response to visual, somesthetic and to auditory stimulationalthough the latter is most effective (Halasz and Ujszaszi 1988). TheK-complex response to auditory (click) stimulation is large and lessvariable during light sleep (stage 2); while during stage 4 SWS there isno sensory-evoked modifications of the electrical activity (Davis et al.1939).” (Velluti, 1997)

“Experimental data gathered using the far field-potential recordingtechnique in humans showed no sleep effects on the brainstem auditoryevoked potentials (Amadeo and Shagass 1973; Picton et al. 1974;Osterhammel et al. 1985; Bastuji et al. 1988). In addition, theconstancy of the response was maintained whether sound stimuli wereeither of high or low intensity (Campbell and Bartoli 1986). Moreover,normal brainstem auditory evoked potentials were observed duringsleep/waking in apnoeic patients (Mosko et al. 1981).” (Velluti, 1997)

“The trigeminal sensory nuclear complex conveys sensory information fromthe face and mouth to higher brain regions such as the thalamus andcortex. In 1965, Hernandez-Peon et al. reported that tactileevoked-field potentials recorded at the trigeminal nucleus level showeda powerful suppression during W [wakefulness] and PS [paradoxical (REM)sleep], while a facilitatory effect was present during SWS [slow wavesleep]. This phenomenon, the increased amplitude of the evoked responseduring SWS, has been seen in most reports of sensory system evoked-fieldpotentials, e.g. visual (Garcia-Austt 1963; Palestini et al. 1965),auditory (Herz 1965; Hall and Borbely 1970), and in the auditory nervecompound action potential (Velluti et al. 1989) as well as in theelectroretinogram (Galambos et al. 1994).” (Velluti, 1997)

“Somatosensory signals are conveyed along two ascending systems in thespinal cord, i.e. the dorsal-column-medial lemniscal system that relaysinformation about tactile sensation and propriocepcion, and theantero-lateral system, carrying chiefly pain and temperature sensations.Studying the modulation of synaptic transmission at the level of thedorsal column nuclei in the lemniscal system during sleep, Pompeiano'sgroup demonstrated that during PS there is a phasic depression of theorthodromic lemniscal response occurring synchronously with REM bursts(Carli et al. 1967) . . . . The incoming somatosensory information fromthe body is transmitted rostrally by neurons located in the spinal corddorsal horn laminae, whose axonal projections comprise a number ofascending pathways, including the spinoreticular, the spinothalamic andthe spinomesencephalic tracts conveying pain, temperature and to a muchlesser extent, tactile sensations. Soja et al. (1993) demonstrated thatthis sensory input changes its characteristics depending on thesleep/wake cycle.” (Velluti, 1997)

“The electrical activity of the olfactory bulb is modulated by thesleep/waking cycle. The waves, bursts of 40-50 c/s simultaneous withrespiration, increase during attention or sniffing and decrease duringSWS to disappear during PS; this phenomenon has been explained by aninhibitory centrifugal control (Hernandez-Peon et al. 1960) . . . .

In humans, only limited data on the topic are available. The existingdata indicate (Badia et al. 1990) that a behavioural awakening reactionoccurs when olfactory stimuli are presented during sleep.” (Velluti,1997)

“These findings might corroborate the hypothesis of the existence of 2separate neural systems integrated in the arousal network and undergoingdifferent modulatory influences.”

Further studies indicate that overall, increasing ventilatory effort maybe the most important stimulus to arousal from sleep, and the stimulusto arousal from hypoxia and hypercapnia may be mediated principallythrough stimulating an increased ventilatory efforts.

These considerations raise the question of possible manipulation of thearousal response to maximize the beneficial effects related tofacilitating resumption of airflow, but minimize the adverseconsequences related to sleep fragmentation and post-apneahyperventilation. These latter effects appear to relate more to corticalthan brainstem arousal.

Furthermore some studies concluded that: “The current findings suggestthat strategies of induced arousal, at an intensity level stimulatingrespiration while avoiding recruitment of the ascending arousal systemand its potential effects of sleep disruption, could have potentialapplication as a therapeutic modality. Apnea was detected by trachealbreath sounds which were picked up by microphone . . . stimulationdecreased the frequency of apnea episodes and the longest apneaduration. This resulted in an increase in arterial oxygen saturation.Moreover stimulation decreased sleep stages I and II, and increasedstages III and IV. These findings suggest that stimulation using theapnea demand-type stimulator may be an effective treatment for OSA”.

Other research has determined that: the Psa (Blood Pressure) and HR(Heart Rate) increased more and the SV (Stroke Volume) decreased more inthe apnea that was terminated by an EEG (cortical) arousal compared withthe apnea without an EEG (subcortical) arousal.

Furthermore externally applied stimulus is reported to cause a “trendamong our subjects to shortening of the apnea immediately after thestimulated apnea; that is, the effect of the tone appeared to extend tothe next apnea. We would hypothesize that the acoustic stimuli did altersleep state and thus arousal threshold such that the immediatelysucceeding apnea might have been more susceptible to concurrentrespiratory afferent stimuli.” This took place in spite of the trend forObstructive Sleep Apneas to increase in both frequency and durationduring a nights sleep.

“Using sound stimulation with 90-dB tones at 625 Hz, 1/1 to 1/5 min ratedelivered by headphones, Levine et al. (1987) found that the number ofnatural arousals decreased during nights with frequent (1/1 min)stimulation resulting into abundant evoked arousals.” (Halasz 2004)

“One animal study reported that the [stage two slow wave sleep] SWS-2(in rats), with high delta wave power, showed the highest arousalthreshold when a non-meaningful sound was used (Neckelmann and Ursin1993).

Conflicting results have been reported concerning sound stimulationeffects on sleep in animals. Continuous high intensity white-noisestimulation resulted in almost complete deprivation of [paradoxicalsleep] (PS) in rabbits (Khazan and Sawyer 1963) while in rats, the samestimulation led to PS reduction without a or edecrease in the amount of[slow wave sleep] (SWS) (Van Twyver et al. 1966).” (Velluti 1997)

“Very interesting results were reported by Buendia et al. (1963) whoobserved that the responsiveness of a conditioned cat to a 5 kHz‘positive’ tone (reinforced with classical and instrumentalconditioning) during wakefulness was characteristic but different ineach sleep phase, measured by the tone's capacity to awaken the animal.”(Velluti 1997)

“During sleep, one normal reaction to any supra-threshold sensorystimulation is a return to a wakeful condition. Moreover, upon sensorystimulation, a special evoked EEG pattern is described (Loomis et al.1938) designated as the K-complex. Appearing in response to sensorystimulation, as well as spontaneously, K-complexes are observed inresponse to visual, somesthetic and to auditory stimulation although thelatter is most effective (Halasz and Ujszaszi 1988). The K-complexresponse to auditory (click) stimulation is large and less variableduring light sleep (stage 2); while during stage 4 SWS there is nosensory-evoked modifications of the electrical activity (Davis et al.1939). Human auditory responses recorded from the vertex have beenreported by several investigators using similar approaches and obtainingsimilar results. In all subjects the major changes in the auditoryevoked response, in changing from the awake state to the four stages ofSWS sleep was a consistent increase in peak to peak amplitude. During PSthe amplitude was lower and approximated that of the awake state. Thelater waves of the response were of longer latency during both sleepphases, SWS and REM (Vanzulli et al. 1961; Davies and Yoshie 1963;Williams et al. 1963; Weitzman and Kremen 1965; Ornitz et al. 1967).Campbell et al. (1992) in a comprehensive review of evoked potentialsand information processing during sleep, arrived at some interestingalthough debatable conclusions. The experimental data gathered using thefar field-potential recording technique in humans showed no sleepeffects on the brainstem auditory evoked potentials (Amadeo and Shagass1973; Picton et al. 1974; Osterhammel et al. 1985; Bastuji et al. 1988).In addition, the constancy of the response was maintained whether soundstimuli were either of high or low intensity (Campbell and Bartoli1986). Moreover, normal brainstem auditory evoked potentials wereobserved during sleep/waking in apnoeic patients (Mosko et al. 1981) . .. . Thus, it is hypothesized that during different CNS states (e.g.sleep) control must be exerted as far as the most peripheral auditoryregions. We are beginning to observe this, both from newly gatheredexperimental data as well as from teleologically evaluating the complexauditory efferent system. The data on the sleep effects on middlelatency auditory evoked potentials (potentials perhaps arising from thereticular formation, thalamus, and primary cortex) are much lessconsistent. While early studies indicated that these components wereeither not affected or only slightly affected by sleep, more recentreports showed marked changes, most notably in the later evokedpotential components (Osterhammel et al. 1985; Erwin and Buchwald 1986;Ujszaszi and Halasz 1986), although see Campbell, Bell and Bastien.(1992). The later components of the evoked potential, also called theslow potentials or late auditory evoked responses, are the most alteredduring sleep. A clear N1-P2-N2 complex exists during W with nodiscernible P1. During SWS and stage 2, N1 is attenuated while P2 mayincrease in amplitude. On the other hand, during PS, N2 becomes largerwhile the general morphology of the late components approaches that ofW. The P3 wave, considered an endogenous potential, is not visible whensubjects are awake and distracted, hence ignoring the auditory stimuli.Similarly, P3 can not be detected during sleep (Campbell et al. 1992)although Bastuji et al. (1990) suggested that P3 may be present duringPS.

The amplitude of the averaged auditory nerve compound action potentialand the microphonic potentials, in response to clicks and tone-bursts,have been reported to change throughout the sleep/waking cycle.”(Velluti 1997)

“80% of the recorded cells changed their firing during binarualstimulation while 85% did so during ipsilateral sound stimulation. Inaddition, shifts in the discharge pattern were observed in 15% of thecells recorded on passing from W to sleep while the most strikingchange, observed in decreasing firing units, was the near-absence ofresponses in PS during the last 40 ms as judged from the post-stimulustime histogram (stimuli: 50-ms tone bursts).” (Velluti 1997)

“The organization of human sleep is extremely sensitive to acousticstimuli and noise generally exerts an arousing influence on it.”(Velluti 1997)

“Auditory sensory gating is a rudimentary physiological assay of thebrain's ability to filter out or ‘gate’ extraneous acoustic information.This phenomenon is generally measured by observing the reduction inmagnitude of particular auditory evoked potentials as a function ofstimulus repetition (i.e. stimulus redundancy). Evoked potentialattenuation of this type has been alternatively interpreted as areflection of the brain's finite ‘recovery function’ (e.g. Davis et al.,1966).” (Kisley 2001)

“Rapid eye movement (REM) sleep is a particularly appropriate candidate‘state’ for the measurement of component P50 sensory gating. During REMsleep, the activity of noradrenergic neurons in the locus coeruleus aregreatly reduced (Hobson et al., 1975), potentially removing theconfounding effect of norepinephrine. Furthermore, the possibleinfluence of selective attention on sensory gating becomes irrelevant ifsubjects are asleep. Waveform measurements necessary to assess gatingcan be achieved because all components of the auditory evoked potential,including P50, are present during REM sleep (Williams et al., 1962;Weitzman and Kremen, 1965). Further, differential processing ofsequential acoustic stimuli occurs during REM sleep as reflected inlater evoked potential components, such as the mismatch negativity(Loewy et al., 1996, 2000; Nashida et al., 2000) and P300 (Sallinen etal., 1996; Cote and Campbell, 1999a,b). Nevertheless, only one previousstudy has examined auditory evoked potential attenuation as a functionof stimulus repetition during REM sleep: Ornitz et al. (1972, 1974)found that component N2—a negative wave occurring about 250 ms afterstimulus onset—exhibits better recovery (i.e. poorer gating) during REMsleep than during waking in healthy children.” (Kisley 2001)

“Electroencephalographic signals were recorded (Neuroscan AcquisitionSystem; Sterling, Va.) from each subject during two separate sessions:one during waking, and one during sleep. Half of the subjects underwentthe waking recording first. For both sessions, the continuouselectroencephalogram (EEG) was recorded from a vertex electrode (Cz)referenced to the right ear, and the electrooculogram (EOG) from abipolar configuration between electrodes directly above and lateral tothe left eye. During sleep recordings, the electromyogram (EMG) was alsorecorded with a bipolar submental configuration. A ground electrode wasattached to the left ear. All electrode impedances were maintained below10 kV. Average auditory evoked potentials were computed from the EEGactivity immediately following acoustic clicks (0.04 ms pulse, filteredbetween 20 and 12 000 Hz), which were delivered through insertearphones. The click intensity was adjusted to 40 dB above eachsubject's hearing threshold (determined by method of limits; thresholdsfor all subjects were within a 10 dB range), separately for each ear.Clicks occurred in pairs (0.5 s inter-click interval), and pairsoccurred every 10 s. For the awake recording, supine subjects wereinstructed to keep their eyes open and still during auditory stimuli(which occurred every 10 s), and to apprise the experimenter of anydifficulty in staying awake or keeping their eyes open. After a 5 minacclimatization, recording began and lasted until 30 min of data hadbeen acquired. Each subject decided during the experiment whetheracquisition continued unabated for 30 min (N=4), or whether this timewas broken up into two 15 min blocks (N=4), or 3 blocks of 10 min each(N=2) . . . .

For acquisition, EEG signals were amplified 5000 times and filteredbetween 0.1 and 200 Hz, EOG amplified 1000 times and filtered between0.1 and 100 Hz, EMG amplified 12 500 times and filtered between 5.0 and200 Hz. Occasionally, a 60 Hz bandstop filter was used to attenuatepower line artifact. All channels were sampled at 1000 Hz. Continuouslyrecorded data were converted from Neuroscan's Scan 4.1 software formatto ASCII format, then imported into the Matlab software package(Mathworks; Natick, Mass.) for further analysis with custom programs.Single trial evoked potentials were isolated from the continuous EEG byaligning the signal with stimulus markers to the nearest millisecond.These trials were filtered with a bandpass (5-100 Hz) that includesthose frequencies which contribute the most power to auditory middlelatency components (Suzuki et al., 1983), and a bandstop filtered at 60Hz. All filters were applied both forward and reverse to eliminate phasedistortion (Matlab's ‘filtfilt’ function).

Continuous recordings were divided into 20 s epochs for scoring of sleepstages, and initially screened for REM sleep periods by simple poweranalysis: the average power in the EEG channel between 12 and 14 Hz(‘spindle’ band), the total power in the EOG channel, and the totalpower in the EMG channel were plotted as a function of time for theentire recording session (e.g. FIG. 1 ). Putative REM sleep episodeswere then easily detected as periods of greatly reduced spindle power,increased EOG power (due to REMs), and reduced submental EMG power (dueto reduced muscle tone). Final determination of sleep stage was achievedby visual inspection of the EEG, EOG, and EMG signals in 20 s epochs,and the application of traditional criteria as described inRechtschaffen and Kales (1968). Average auditory evoked potentials werecomputed from EEG signals recorded during the initial 30 min of thefirst REM episode of the night that lasted 30 min or longer. A ‘REMepisode’ was considered to begin when two consecutive 20 s epochs werescored as REM sleep, and end when 3 or more consecutive epochs werescored as non-REM sleep or waking. A REM episode defined in this mannercould include epochs with movement artifact and arousals as long as thesubject returned to REM sleep within two epochs . . . .

Pairs of clicks (0.5 s inter-click interval) were presented every 10 sthroughout the recording session, and average evoked potentials computedseparately for each click of the pair. For each of the individual evokedpotential components, the magnitude of evoked response to the second(‘test’) click of a pair was then compared with the magnitude of evokedresponse to the first (‘conditioning’) click. Specifically, a ratio ofthe magnitudes, the test/conditioning or ‘T/C’ ratio, was computed toquantify sensory gating. A T/C ratio close to 0 indicates robustsuppression (very small test response compared with conditioningresponse) and a T/C ratio of 1 indicates essentially no sensory gating(test and conditioning responses were comparable in magnitude). In thegeneral population, T/C ratios for component P50 range between 0 andwell over 1, but are generally below 0.4 for subjects without a personalor family history of psychosis (Siegel et al., 1984; Waldo et al., 1994). . . .

Auditory evoked potential components were defined as follows: P30,positive wave, peaking between 25 and 45 ms; P50, positive, peak 45-65ms; and N100, negative, first trough greater than 75 ms . . . . Tomaintain consistency with previous sensory gating literature, magnitudesof these components were measured from preceding trough to peak (P30 andP50: Nagamoto et al., 1989) and from preceding peak to trough (N100).”(Kisley 2001)

“In contrast to Erwin and Buchwald (1986b) who reported a virtualabsence of component P50 during stage II sleep for all 14 of theirsubjects, we found clear evoked potential components corresponding toP50 in 8 of our 10 subjects during non-REM (mostly stage II) sleep.Further, we found the mean amplitude of P50 during non-REM sleep to beapproximately equal to that for REM sleep. Methodological elements whichdiffered between our studies might be responsible for the discrepancy.Erwin and Buchwald (1986b) filtered auditory evoked potentials between10 and 300 Hz, whereas we filtered between 5 and 100 Hz. Since evokedpotentials were recorded with a wide bandpass (0.1-200 Hz) for thepresent study, and subsequently filtered digitally, we are able tocompare the effect of different cut-off frequencies on the magnitude ofwave P50. The example shown in FIG. 4A demonstrates that a filter verysimilar to that used by Erwin and Buchwald (10-200 Hz) does not reducethe amplitude of P50 evoked during non-REM sleep. Thus, the differencein filter parameters probably cannot explain the discrepancy in resultsbetween the present study and that of Erwin and Buchwald (1986b). Wefeel the difference between acoustic stimulation paradigms utilized inthe two studies is more likely to be responsible for the disparatefindings regarding the magnitude of wave P50 during non-REM sleep. Thecritical variable is probably the inter-click interval. Erwin andBuchwald (1986b) presented auditory clicks in trains at 1 Hz, whereas weemployed the paired-click paradigm. Average evoked potentials werecomputed from all evoked responses in a click-train for the former(inter-click interval, 1 s), and only from the conditioning evokedresponses for the latter (interclick interval, 10 s). Like Erwin andBuchwald, Jones and Baxter (1988) reported the disappearance ofcomponent P50 during non-REM sleep when clicks were presented in rapidtrains (5 Hz), even though very wide-band filters (0.3-3000 Hz) wereapplied to the evoked potential signal. In comparison, studies usingclick-trains at slower rates of presentation (0.5 Hz or less) haveconsistently reported the robust presence of component P50 across allsleep stages, including II, III, and IV in adults (Williams et al.,1962; Weitzman and Kremen, 1965; Kevanishvili and von Specht, 1979) andchildren (Barnet et al., 1975). To summarize, vertex component P50appears to be measurable under non-REM sleep for most subjects inresponse to the conditioning click for the paired-click paradigm, andalso in response to clicks during the click-train paradigm for rates of0.5 Hz or less, but not for rates of 1 Hz or more.” (Kisley 2001)

The kind of stimuli provokes different responses in human subjects:“Previous studies using single-modality paradigm have shown that sensorygating systems, which select relevant sensory information, remainfunctional during sleep.” Halasz et al., 2004; Kisley et al., 2001;Velluti, 1997; which are hereby incorporated by reference.

“In humans, relevant stimuli (e.g. sound >65 dB, one's own name,experimental noxious stimulation) induce arousal response morefrequently and results in more intense response compared with irrelevantstimuli . . . . Simultaneous multi-modality sensory inputs from bodysurface and from other organs (e.g. ear) not only increase the amount ofsensory inputs but also can maximize the relevance of stimuli.”

Central Sleep Apnea results from the brain failing to signal the musclesto breathe. The neural drive to the respiratory muscles discontinues fora brief period of time. These transients may continue throughout thenight for periods from ten seconds to as long as 2 to 3 minutes. Thephysiological effects are similar to those of Obstructive Sleep Apnea.

Mixed Sleep Apnea is a combination of Obstructive Sleep Apnea andCentral Sleep Apnea.

There are several known treatments for Sleep Apnea. They consist ofphysical, electrical, and mechanical methods, surgery, and attempts atpharmacological treatment. The treatment regimen is tailored to theindividual, and is based on the medical profile of the patient beingtreated.

The most common effective treatment for patients with sleep apnea isnasal continuous positive airway pressure (CPAP). In this form oftreatment, the patient wears a mask over the nose while sleeping. Themask is connected to a compressor that creates a positive pressure inthe nasal passages. The continuous positive airway pressure systemprevents the airway from closing or becoming obstructed during sleep.The air pressure from the continuous positive airway system is constant,and can be adjusted to best suit the individual's apnea condition. Theair pressure in the continuous positive airway pressure system must beadjusted so that it maintains an open airway in the patient during allperiods of sleep, but does not provide excessive pressure such that thedevice is bothersome to the patient. U.S. Pat. No. 4,655,213 disclosessleep apnea treatments based on the principles of continuous positiveairway pressure. There have also been recent attempts at varying theapplied pressure to increase the effectiveness of continuous positiveairway pressure treatment. U.S. Pat. Nos. 4,773,411 and 6,539,940disclose such techniques. The disclosures of these United States patentsare incorporated herein by reference.

Another treatment for sleep apnea in certain patients involves the useof a Dental Appliance to reposition oral structures such as the tongueand the lower jaw. This form of treatment is typically performed by adentist or dental specialist such as an orthodontist.

Surgery has also been performed to treat sleep apnea. In some surgicaltreatments, the size of the airway is increased. These surgicalprocedures contain elevated levels of risk in comparison to othertreatment methods, and often times are not entirely effective. The formof surgery to be undertaken is specific to the patient and the patient'smedical profile. The removal of obstructive tissue in the airway such asadenoids, tonsils or nasal polyps is a common form of surgical treatmentfor sleep apnea. The surgical correction of structural deformities isalso a common form of surgical treatment for sleep apnea.

Another form of surgical treatment for sleep apnea isuvalopalatopharyngoplasty. This procedure removes excess tissue from theback of the throat, such as tonsils, uvula, and part of the soft palate.Somnoplasty is also being investigated as a possible treatment for sleepapnea. Somnoplasty uses radio waves to reduce the size of some airwaystructures such as the uvula and the back of the tongue.

Other forms of surgical intervention for sleep apnea includemaxillo-facial reconstruction. Another form of surgical treatment forpatients with severe and life threatening sleep apnea is Tracheostomy.This procedure involves making a small hole in the windpipe thataccommodates a tube. The tube is opened only during sleep, and allows apatient to take air directly into the lungs, effectively bypassing anyupper airway obstructions. Tracheostomy is an extreme procedure that isvery rarely used except for cases of imminent life threatening sleepapnea.

Attempts at pharmacological treatment for sleep apnea have includedrespiratory stimulants such as theophylline, acetazolamide andmedroxy-progesterone, and adenosine. Drugs that stimulate brain orcentral nervous system activity, such as naloxone and doxapram, havealso been used in an attempt to treat sleep apnea. Other drugs that acton the neurotransmitters involved with respiration have also been usedin an attempt to treat sleep apnea. These drugs include serotonin,dopamine, tryptophan, fluoxetine, and others.

More recently, systems have been developed for the purpose of clearingupper airway passages during sleep using the electrical stimulation ofnerves or muscles. In some cases, these systems require surgicalimplantation of sensors and associated electronics that detect whenbreathing has ceased and then stimulate the breathing process. Somehybrid systems have been developed that require surgical insertion ofone or more sensors plus external equipment for monitoring the breathingprocess or moving the obstruction when breathing ceases.

An apparatus has been patented a means for detecting the onset of asleep related disorder using pulse rate and blood oxygen contentinformation as measured by the device; U.S. Pat. No. 7,387,608 disclosessleep apnea treatments based on those principles. The disclosures ofthese United States patents are incorporated herein by reference.

An apparatus has been patented a means for detecting the onset of asleep related disorder using a multiplicity of microphones. Theapparatus has the microphones emplaced within a collar worn around theneck of the patient. The apparatus detects breathing sounds, and in anembodiment when it detects breathing that is “substantially differentfrom the recorded at least one signal pattern that is associated with anormal breathing pattern of the person; and creating a stimulus to theperson's neck muscles to cause the person to move the person's neckmuscles to move the person's head backwards to restore normal breathingbefore cessation of breathing occurs”, as disclosed in U.S. Pat. No.6,935,335. The disclosures of these United States patents areincorporated herein by reference.

SUMMARY OF THE INVENTION

The present invention is directed to a apparatus and method fordetecting and treating Sleep Apnea and Hypopnea by terminating a SleepApnea event or Hypopnea episode within seconds of detection.

The invention develops through a Method a Referential set of Parametersspecific to the respiration patterns of the specific patient (ratherthan defining and applying Generic Trigger point Parameter as is thecase with other inventions). The multiplicity of Signal Parameterscombined with a Fuzzy Control System is more adaptable to the changes ofRespiration that occurs during the course of the night. Changes ofRespiration which might be interpreted by other inventions such as thosewho use averaging or weighted moving averaging of invention anddetermined to be a reversion to a Respiration pattern that is normal forthis specific patient. Normal for the patient is established by theProcessing of the Referential set of Parameters within the Fuzzy ControlSystem.

The inventions method of using both the root-mean-square deviation of aparameter and the parameters' mean, as opposed to simply averaging orweighted moving averaging of the parameter, to establish a referencepoint for determination of a parameters' out of bound condition, is asuperior method for detecting Apnea events or Hypoxia episodes.

In accordance with the present invention, there is provided a wearable,belt like, apparatus for the treatment of Sleep Apnea events andHypopnea episodes containing a Microphone and a Plethysmograph. TheMicrophone and Plethysmograph generate signals that are representativeof physiological aspects of respiration. The signals are transferred toan embedded computer. The embedded computer extracts the sound ofbreathing and the sound of the heart beat by the means of Digital SignalProcessing techniques. The embedded computer has means for determiningwhen respiration parameters falls out of defined boundaries for therespiration parameters. This method is for the real-time detection ofthe onset of a Sleep Apnea event or Hypopnea episode. The embeddedcomputer supplies stimulation signals upon the determination of a SleepApnea event or Hypopnea episode to initiate an inhalation. Thestimulation is provided in a manner so as to avoid the initiation of acortical (EEG) arousal and vagal withdrawal of the parasympathetic toneto the heart. The stimulus is applied to the patient by a cutaneousrumble effects actuator and audio effects broadcasting. The actuator isembedded within the invention.

It is a primary object of the present invention to provide a system andmethod for detecting and terminating an Sleep Apnea event and Hypopneaepisode, within seconds of the detection, in a manner that will decreaseor eliminate hypoxia, hypercapnia and the disturbance of pulmonaryhemodynamics respirations as an Apnea Event or Hypopnea episode could beprocessed by the present invention.

Technical Problem

Positive Airway Pressure (PAP) systems remain the most effectivetreatment for sleep apnea. Many patients, however, cannot tolerate thePositive Airway Pressure systems and associated apparatus. Commoncomplaints include discomfort with the applied pressure, discomfort withthe mask and equipment, nasal irritation, nasal stuffiness andcongestion, airway dryness, mask air leaks and noise, entanglement,claustrophobia, noise of the PAP machine, headaches, abdominal bloating,sore and irritated eyes, and an overall discomfort with the machinery.The noise and general obtrusiveness of the PAP apparatus are oftendisruptive to another person sleeping with the user.

A significant minority of the people for whom PAP is prescribed(estimated to be 30% to 50%) refuse to use it. A study determined thatof the patients who use PAP treatment, it is estimated that 34% use itintermittently (4 nights per week) and/or remove it for part of thenight (for this group median nightly usage is 3.1 hours).

Beyond the initial cost of the PAP (>U$500.00) there is a continuingcost of replacement masks. It is recommended that masks be replacedevery six months (=>U$100.00/mask).

A study determined that Dental Appliances was successful in treating OSAin an average of 52% of treated patients, with success defined as nomore than 10 apneas or hypopneas per hour of sleep. Treatment adherenceis variable with patients reporting using the appliance a media of 77%of nights at 1 year.

A Dental Appliance typically has a cost in excess of U$1000.00.

Surgery has inherent risks: its' cost is high, its' success rates varyand over a period of time its' effectiveness fades.

Pharmacological treatments for sleep apnea have not achieved anyconsistent levels of effectiveness, and often contain side effects.

Systems that clear the upper airway passages during sleep using theelectrical stimulation of nerves or muscles. These systems may producepositive results but they also have associated risks due to surgery, mayneed replacement at later times (requiring additional surgery), and mayhave higher costs and lower reliability than the more traditionaltreatments. In addition, the hybrid systems also have the accompanyingphysical restrictions and accompanying disadvantages associated withconnections to the external equipment.

An apparatus whose means for detecting the onset of a sleep relateddisorder relies on blood oxygen content information cannot determine theonset of a sleep order in real time. Oxygen saturation leveldiminishment always lags the cessation of breathing because it takestime for the as oxygen in the bloodstream to used up by bodilyprocesses. Hypoxia and hypercapnia will occur.

An apparatus whose sole means for detecting the onset of a sleep relateddisorder relies on detecting the sounds of breathing can be confused byextraneous noises, coughing, wheezing and other internally generatedbiologic noises. In addition in order for both the microphones andstimulus devices to work most effectively they must be in close contactwith the neck and this constriction may prove to be unacceptablyuncomfortable to the patient.

Many of these devices provide a single type of auditory stimulus (afixed tone of varying intensity) and/or mechanical stimulus (avibrator).

For example, U.S. Pat. No. 7,387,608 discloses such techniques. It isClaimed that: “The method of arousing the patient from sleep at theonset of a sleep apnea event will decrease or eliminate the occurrenceof sleep apnea, arrhythmia, and partial epilepsy over time.”

These methods of stimulus may prove to be initially effective inreducing the numbers of Apnea events through a process of Conditioning.However, with Conditioning there co-exists Habituation. These are twointeracting psychological phenomena with a number of similarities. InConditioning, an animal is exposed to some events, and as a consequence,it learns to associate a certain behavior with a specific situation. InHabituation too, an event occurs repeatedly, but in this case, thereaction of the animal wanes with repeated exposure.

The dynamics of Habituation is very similar to the extinction of aresponse that has previously been learned during Conditioning. In bothcases, the response becomes less probable or weaker with each occurrencewith the event. There is one large difference between the twosituations, however. In extinction, a learned response is weakened, butin Habituation the reaction that dies away is typically an innateorienting reaction. Conditioning may indeed lead to extinguishment ofSleep Apneas events or the opposite may occur; Habituation might lead tothe patient ignoring the stimulus. If Habituation occurs then SleepApnea events would continue until they spontaneously terminate.

Solution to Problem(s)

Therefore, there is a need in the art for an improved system and methodfor treating Sleep Apnea events and Hypopnea episodes. In particular,there is a need in the art for a system and method that does not createother types of sleep disturbing effects, does not require surgicalimplementation, does not involve the use of a complicated apparatus,does not include the use of pharmaceuticals, does not require theintervention of health professionals, and does not have the high costsassociated with some of the types of treatments currently in use.

Therefore, there is a need for a system and method for treating SleepApnea event and Hypopnea episode by terminating a Sleep Apnea event andHypopnea episode in real time that minimizes the disturbance topulmonary hemodynamics.

Therefore, there is a need for a system and method for treating SleepApnea event and Hypopnea episode that is easy to use by the patient,comfortable, and less expensive than other methods of treatment.

Advantageous Effects of Invention

An Advantageous Effect of Invention is the superior method of detectionof Sleep Apnea events and Hypopnea episodes:

Using the standard deviation of a parameter in conjunction with theparameters' mean and a rules based processing (Fuzzy Logic) as opposedto using only a parameters' mean as a reference point for determinationof a parameters' out of bound condition (excursion) leads to thediminishment of the occurrence of the invention detecting a false Apneaevent or Hypoxia episode.

In the situation where the parameters' mean is the only reference, asingle excursion beyond an established limit leads declaration of anApnea event or Hypoxia episode. Conversely, with this method of theinvention, when an excursion is determined, a further determination isperformed to establish if the excursion is smaller than every member ofthe set of parameters that were gathered during the Self-calibrationsprocesses. For while an excursion might be smaller than the mean of theparameter that was calculated by the processes the Self-calibrations, itmight be greater than any single parameter that formed the set ofparameters that were determined to be “normal” for this specific patientand which formed the reference set of parameters.

The use of rules based processing (Fuzzy logic) allows the invention toevaluate the significance of excursions and make decisions as to whetheras excursion merits initiating Stimulus.

The invention analyzes a multiplicity of parameters derived fromredundant apparatus to detect respirations. The use of rules basedprocessing (Fuzzy logic) allows the invention to evaluate thesignificance of excursions of any single parameter or any combination ofparameters from the redundant apparatus and make decisions as to whetheras excursion merits initiating Stimulus.

Another Advantageous Effect of the Invention is its' ease of use. Manyof the patients who would use the invention are both obese and old(er).The invention is simple to don. The invention uses plain languagecommands to guide the patient in to properly position the invention.

Another Advantageous Effect of the Invention is it is not anencumbrance. The sleeping patient is not physically constrained. This isimportant in light of the fact that many of the patients have enlargedprostrates which, in many cases, necessitates frequent urination duringthe night.

Another Advantageous Effect of the Invention is that it is lessexpensive that most other solutions. From the perspective of overallcosts:

It does not require the programming of baseline parameters. Baselineparameters that have to be entered into an apparatus would require thatthere be an evaluation of the results from the patients' polysomnographyand using a method to establish baseline criteria. The invention selfdetermines the baseline parameters, thereby eliminating any requirementfor determination of baseline parameters performed outside of the systemor entry of baseline parameters into the system.

There are no replacement components. Other devices require periodicreplacement of key components, at a considerable expense.

The invention is no more expensive that the average price of the mostpopular form of treatment for Obstructive Sleep Apnea (CPAP).

Another Advantageous Effect of the Invention is that it can be used inconjunction with the most popular form of treatment for ObstructiveSleep Apnea (CPAP) or as an alternate, independent form of treatment.There is a significant minority or patients who use the CPAPintermittently. Using the invention during those times that the patientis not using CPAP would continue the benefit to the patient that isrealized by maintaining normal blood oxygen and carbon dioxide levels.

Another Advantageous Effect of the Invention is it is self-adapting; itself-determines referential baselines for the specific patients' normalrespiration patterns. One of the definitions of Obstructive Sleep Apneais interruptions in airflow of at least 10 seconds. The invention may,depending on the normal respiration pattern of that patient, establish adifferent baseline as to what an interruption of airflow in secondswould be.

By immediately applying a Stimulus that has been determined to initiatean inhalation at the lowest level of stimulation, the effects on thephysiology of the patient of the Apnea event or Hypoxia episode will beminimized.

Another Advantageous Effect of the Invention is that there are devicesthat ramp up the stimulus (be it the frequency of a mechanical vibratorand/or audio and/or amplitude) until respiration is restored. This takestime, in which case the deleterious effects of declining blood oxygenand increasing blood carbon dioxide accrue, and if it overshoots (therebeing a delay between the time a stimulus is applied and the reaction ofthe patient to it) it could lead to a heightened waking than is requiredto terminate the Apnea event or Hypoxia episode.

Another Advantageous Effect of the Invention is that it isself-adapting; it self-determines referential baselines for the type ofStimulus that is required to terminate an Apnea event or Hypoxiaepisode. Research has shown that the amount of stimulus required toinitiate an inspiration changes in cycles during sleep. The inventioncontinuously evaluates the Stimulus required to terminate an Apnea eventor Hypoxia episode.

Another Advantageous Effect of the Invention is that it can supply avery wide range of Stimulus. It has a multiplicity of embedded Audiofiles and Haptic pattern files, each with a distinct irritation index.The invention will determine which files produce the Stimulus requiredto initiate an inhalation at the lowest level stimulation. Since thereare many file combinations that will produce the Stimulus required toinitiate an inhalation at the lowest level stimulation, the inventioncan avoid Habituation while maintaining the benefit of Conditioning.

BRIEF DESCRIPTION OF DRAWINGS

The invention will be described by reference to the following drawings,in which like numerals refer to like elements, and in which:

FIG. 1 is a top and Bottom External view of the present invention;

FIG. 2 is a Cross-section view;

FIGS. 3A, 3B, and 3C are Block Diagrams of the manner in whichMicrophone and Plethysmographic sensor data is converted into Signals;

FIG. 4 is a Block diagram of the Electronic and Electrical elements ofthe invention;

FIGS. 5A, and 5B are Block Diagrams of the Training and MonitoringProcesses;

FIG. 6 is a Block Diagram of the Fuzzy Control System;

FIG. 7 is a diagram of a Patient wearing the invention; and

FIG. 8 is a Block Diagram of Portrait Development.

DESCRIPTION OF EMBODIMENTS

Accordingly, embodiments of the present invention are provided that meetat least one or more of the following objects of the present invention.

In one embodiment, a wireless auditory prompter (Bluetooth Earbud) ismounted in the patient's ear and is activated by the stimulation signalto emit an acoustic stimulus which is heard by the patient but isinaudible to others. This embodiment provides a sound to initiateinhalation without requiring other intervention.

In another embodiment, a wired auditory prompter is mounted in thepatient's ear and is activated by the stimulation signal to emit anacoustic stimulus which is heard by the patient but is inaudible toothers. This embodiment provides a sound to initiate inhalation withoutrequiring other intervention.

In another embodiment, a loud speaker is embedded within the inventionand is activated by the stimulation signal to broadcast an acousticstimulus which is heard by the patient. This embodiment provides a soundto initiate inhalation without requiring other intervention.

In another embodiment, the computer detects the absence of a heartbeatand activates an audible alarm by the loud-speaker embedded within thepresent invention.

In another embodiment, the computer has means to store the calculatedamplitude, periodicity, and duration of respiration for each respirationof the collection of known good respirations from the firstself-calibration in embedded memory.

In another embodiment, the computer has means to store the calculatedvalues and parameters in embedded memory.

In another embodiment, the computer has means to store the time(s) inwhich a Sleep Apnea event and Hypopnea episode occurs in embeddedmemory. In another embodiment, the computer has means to store thetime(s) in which a Sleep Apnea event and Hypopnea episodes areterminated in embedded memory.

In another embodiment, the computer has means to export the calculatedvalues and parameters from embedded memory to other devices.

In another embodiment, the computer has means to export the time(s) inwhich a Sleep Apnea event and Hypopnea episode occurs and from embeddedmemory to other devices.

In another embodiment, the computer has means to export the time(s) inwhich a Sleep Apnea event and Hypopnea episode are terminated fromembedded memory to other devices.

In another embodiment, the computer has means to import modifications ofthe computer programs from other devices.

In another embodiment, the computer has means to import modifications ofthe computer program that comprises the rules based processing (FuzzyLogic) from other devices.

In another embodiment, the plethysmographic sensor can be implementedusing a string potentiometer.

In another embodiment, the plethysmographic sensor can be implementedusing strain gauges.

In another embodiment, the plethysmographic sensor can be implementedusing accelerometers.

In another embodiment, the plethysmographic sensor can be implementedusing Hall Effect components.

In another embodiment, the plethysmographic sensor can be implementedusing LEDS and Photo detectors.

In another embodiment, the plethysmographic sensor can be implementedusing ultrasonic sensors.

In another embodiment, there might be a plurality of microphones.

In another embodiment, the mechanical tactile sensory stimulator may beimplemented using a Haptic Display.

In another embodiment, the mechanical tactile sensory stimulator maybeimplemented using a Haptic Display comprising shape memory springs.

In another embodiment, the mechanical tactile sensory stimulator maybeimplemented using a Haptic Display using multiple actuators.

In another embodiment, the mechanical tactile sensory stimulator maybeimplemented using a Haptic Display comprising rotating drums.

In another embodiment, the mechanical tactile sensory stimulator maybeimplemented using a Haptic Display comprising electroactive polymers.

In another embodiment, sensory stimulation may be applied optically bythe donning of a device that is worn over the eyes and in which LEDsshine light through the eyelids into the pupils.

The foregoing has outlined rather broadly the features and technicaladvantages of the present invention so that those skilled in the art maybetter understand the detailed description of the invention thatfollows. Additional features and advantages of the invention will bedescribed hereinafter that form the subject of the claims of theinvention. Those skilled in the art should appreciate that they mayreadily use the conception and the specific embodiment disclosed as abasis for modifying or designing other structures for carrying out thesame purposes of the present invention. Those skilled in the art shouldalso realize that such equivalent constructions do not depart from thespirit and scope of the invention in its broadest form.

Before undertaking the Detailed Description, it may be advantageous toset forth definitions of certain words and phrases used throughout thispatent document: the terms “include” and “comprise” and derivativesthereof mean inclusion without limitation; the term “or,” is inclusive,meaning and/or; the phrases “associated with” and “associatedtherewith,” as well as derivatives thereof, may mean to include, beincluded within, interconnect with, contain, be contained within,connect to or with, couple to or with, be communicable with, cooperatewith, interleave, juxtapose, be proximate to, be bound to or with, have,have a property of, or the like; and the term “controller” means anydevice, system or part thereof that controls at least one operation,such a device may be implemented in hardware, firmware, or software, orsome combination of at least two of the same. Definitions for certainwords and phrases are provided throughout this patent document. Those ofordinary skill in the art should understand that in many, if not most,instances, such definitions apply to prior, as well as future uses ofsuch defined words and phrases.

“Measurement” by the Computer in this application is defined as anAnalog-to-Digital Conversion. The derivative of Analog-to-DigitalConversion is a numeric value that is representative of the SignalsAmplitude at the time that the Measurement is made. Those skilled in theart will understand the method of using Analog-to-Digital conversion.

“Processing”, “Process”, “Monitoring”, and “Method” are usedinterchangeably in this document and are collectively defined as theapplication of software programs that are resident within the Computeras means or manner of procedure to accomplishing something. The meansand reasons for the Processing will be addressed in detail within thisdocument.

“Stationary” or “quasi-stationary” signals are those in which thestatistical distribution of frequencies does not change significantlyover the time scale of interest.

“Nonstationary” signals are those whose statistical frequencydistribution changes significantly over the time scale of interest.

“Naturalistic” sounds are sounds that are naturally-occurring or thatmimic naturally-occurring sounds. Naturalistic sounds are nonstationaryand have logarithmically distributed spectrotemporal modulations, ascompared with the linearly distributed spectrotemporal modulations ofsounds that are not naturalistic.

Other objects and features of the present invention will become apparentfrom the following detailed description considered in conjunction withthe accompanying drawings. It is to be understood, however, that thedrawings are designed solely for purposes of illustration and not as adefinition of the limits of the invention, for which reference should bemade to the appended claims.

For a general understanding of the present invention, reference is madeto the drawings. In the drawings, like reference numerals have been usedthroughout to designate identical elements.

In accordance with this present invention, there is provided anapparatus and method for the diagnosis and treatment of Sleep Apnea andHypopnea. In one embodiment of the invention, the respirations of thepatient are monitored during sleep by the apparatus, which acts as amonitoring system to detect and treat Sleep Apnea events and Hypopneaepisodes in the patient. The monitoring system is comprised of anintegrated plethysmographic, an integrated microphone, an integratedcomputer and software program, and methods for applying stimulus to thepatient such as an integrated loud speaker, wired and wireless audio,and an integrated rumble effects actuator. The invention is a wearable,belt-like device, the device is fitted around the Thorax or Abdomen of apatient.

At the onset of a Sleep Apnea event or Hypopnea episode the respiratoryinduced movement (expansion and contraction) of the Thorax and/orAbdomen are significantly reduced. In addition, the movement of air intothe lungs is significantly reduced. These decreases are indicators of anonset of a Sleep Apnea event or Hypopnea episode. During sleep, it isnormal for the patients' respiration parameters for amplitude,periodicity, and duration of respiration to vary. Discerning betweenthose normal variations in the parameters (for amplitude, periodicity,and duration of respiration during sleep) and abnormal variations inparameters (for amplitude, periodicity, and duration of respirationlevels), is performed using a software program that compares thoseparameters gathered by monitoring parameters (for amplitude,periodicity, and duration of respiration during sleep) to thoseparameters (for amplitude, periodicity, and duration of respiration)gathered before the patient fell asleep. This method accuratelyidentifies the onset of a Sleep Apnea event or Hypopnea episode andeliminates false determinations.

The embedded computer's software program uses rules based processing(Fuzzy Logic) to determine when Stimulation is to be applied in order torestore airway patency (by inducing inspiration).

When the patient's respiration parameters are determined by the rulesbased processing (Fuzzy Logic) as showing the onset of an Sleep Apneaevent or Hypopnea episode Stimulation is provided.

The present invention may use historical data, software programs,algorithms or subroutines to assist with the determination of the rulesbased processing (Fuzzy Logic) that are appropriate to the patient. Theembedded computer's software program uses rules based processing (FuzzyLogic) to determine the least amount of Stimulation required to induceinspiration.

The Stimulation is in the form of audio signals and by a cutaneousrumble effects actuator. Rules based processing (Fuzzy Logic) determinethe least amount of Stimulation required to induce inspiration.

FIGS. 1 through 8 , discussed below, and the various embodiments used todescribe the principles of the present invention in this patent documentare by way of illustration only and should not be construed in any wayto limit the scope of the invention. Those skilled in the art willunderstand that the principles of the present invention may beimplemented in any suitably modified system for detecting andterminating an obstructive sleep apnea event.

FIG. 1 illustrates one embodiment of the present invention showingExternal views, Top and Bottom.

The embodiment of the present invention that is illustrated in FIG. 1has Microphone 125 capable of detecting sounds within the airway ofpatient (not shown). One type of microphone that is suitable for use inthe present invention is the electret microphone. Microphone 125 isattached to the Housing 145 and Housing 145 is detachably fastenedaround the Thorax or Abdomen of the patient (not shown) with a Belt 165and Velcro clasp (not shown in FIG. 1 ). Housing 145 is fastened aroundthe Thorax or Abdomen of the patient (not shown) so that Microphone 125is positioned adjacent to the lungs and in contact with the patient (notshown on FIG. 1 ).

LEDs 115 & 120 are Status indicators. The emitted color that the LEDsdisplay are indicative of operational conditions of the presentinvention.

Buttons 105 & 110 control the operations of the present invention.

The Microphone 125 is capable of generating signals representative ofthe sounds of breathing of person 120. When Microphone 125 detectssounds of breathing, it generates a signal. The signal generated by theMicrophone 125 is transferred via an individual microphone signal lineto signal processing circuitry 200 (shown in FIG. 3 ) contained withinHousing 145.

FIG. 2 is a cross-section (side view) of the present invention.

It illustrates that belt 265 has one end attached to Housing 245. Theother end of belt 265 enters Housing 245 and is attached to Shuttle 270and too Spring 290. Shuttle 270 travels within Guide 275. Shuttle 270 isattached to Wiper 280. Wiper 280 is an attachment of MembranePotentiometer 285.

The expansion of the Thorax or Abdomen during inspiration causes Belt265 to pull on Shuttle 270 moving it from its' rest position. Shuttle270 moves within Guide 275 and deforms Spring 290. The movement ofShuttle 270 also moves Wiper 280. Wiper 280 is pressed down on the toplayer of Membrane Potentiometer 285, which in turn touches the bottomlayer of Membrane Potentiometer 285. The touching of the upper and lowerlayer of Membrane Potentiometer 285 creates a voltage divider circuit.The output is voltage. The voltage is a direct inferential reading ofthe magnitude of the expansion or contraction of the Thorax/Abdomen atany time. The Computer processes the voltage as a Signal. The Signaloutput of Membrane Potentiometer 285 varies in direct proportion to theposition of Shuttle 270 within Guide 275.

When an exhalation occurs the Thorax or Abdomen contracts, releasingtension on Shuttle 270. Spring 290 moves Shuttle 270 back towards itsrest position within Guide 275. Those skilled in the art will understandthe method of using Membrane Potentiometers to sense position. Thecutaneous rumble effects actuator 200 is attached to the Housing 245.

The collection of elements of FIG. 2 makeup the IntegratedPlethysmographic Sensor.

FIG. 3 is a Block Diagram of the manner in which Microphone andPlethysmographic sensor data is converted into Signals.

Referring now to FIG. 3A the Block Diagram is illustrative of the Signalthat is outputted from the Integrated Plethysmographic Sensor 301.Buffer 302 conditions the voltage Signal from Plethysmographic Sensor301. The voltage Signal from Buffer 302 is the Thorax/Abdomen MovementSignal 303. The Computer (not shown in FIG. 3 ) Processes the Signal303.

Referring to FIG. 3B the Block Diagram is illustrative of the Processthat the Signals of Breathing Sounds 313 and Heart Beat Sound 312 thatare extracted. The Microphone 304 detects a multiplicity of AudioSignals. The multiplicity of Audio Signals are comprised of the Audiocomponents of biologic processes (Heart Beats, audio component of theturbulence that occurs in the human respiratory system duringrespiration, bowels, snoring, wheezing, yawning, coughing, etc) andexternal interference artifacts. The multiplicity of signals forms aspectrum of Audio frequencies. The elements of the Block Diagram asrepresented in FIG. 3B (Buffer 305, Bandpass Filter 306, EnvelopeDetection 307, Log 308, Sum 309, Integrator 310, and Output Scaling 311)act in concert to filter out the extraneous signals so as to export onlythe Signals of Respiration 313 and the Signals of the Beating Heart 312.

The process is further detailed in the technical paper: Eder, Derek etal. ‘Detection and Analysis of Respiratory Airflow and Snoring SoundsDuring Sleep Using Laryngeal Sound Discrimination (LSD)’ in 1992 Vol.14. Proceedings of the 14^(th) Annual International Conference of theIEEE Engineering in Medicine and Biology Society. Volume 14, Part 6, 29October-1 Nov. 1992 Page(s):2636-2637, which is hereby incorporated byreference. This paper describes “a method that is designed to resolvesounds produced by respiratory activities that are commonly distributedat either extreme of a greater than 90 dB amplitude range. The basis ofour method, non-linear dynamic range compression, is well known and isoften applied in audio sound processing. Our method was specificallydesigned to provide measures of: (1) relative volumetric changes inairflow during hypopnea and apnea, (2) parametrization of respiratoryphase timing and (3) quantitative measures of snoring intensity . . . .

Respiratory airway sounds are transduced by a miniature microphone thatis placed over the lateral aspect of the cricoid cartilage at the levelof the larynx. This microphone placement is optimal for the minimizationof cardiac sounds from the carotid arteries. The microphone element is aminiature electret condenser type with a specified flat frequencyresponse of 20-20,000 Hz. We have encased the microphone element in asmall plastic shell with a 2 mm airgap between the microphone and theskin. This airgap cavity is completely closed, without a pressureequalization port . . . the closed cavity design affords moresensitivity and a greater rejection of environmental sound . . . . Themicrophone shell has a 20 mm lip to facilitate attachment to the skinwith a double-sided medical adhesive tape ring.

The amplitudes of cardiac sounds detected by the laryngeal microphoneoften equal or exceed those of respiration, and would present aformidable confound to the detection of respiratory sounds if they werenot removed. Fortunately, there is little significant spectral overlapbetween cardiac sounds and respiratory airflow sounds. Cardiac soundspredominate below 100 Hz and are effectively removed with low-orderhigh-pass filtering that comers at 200 Hz. While the spectra of cardiacsounds and snoring may overlap, their great difference in amplitudesallows uncompromised detection of snoring even after highpass filtering.We have implemented a three-pole Cauer filter for cardiac soundrejection. This filter stage also eliminates any SO/60 Hz power mainsnoise introduced into the system.

Because the LSD method does not incorporate frequency domain analysis,we are able to preserve the desired information content of therespiratory signal in its amplitude envelope. This enables thedigitization of the LSD signal at sampling rates below 25 samples/sec.The sound envelope is recovered using full-wave rectification andlow-pass filtering. Prior to rectification, the output of the cardiacsound filter is low-pass filtered at approximately 5 KHz to remove anypotential high frequency noise such as RFI. Dynamic range compression ofapproximately 90 dB is effectively obtained by a logarithmictransformation of the respiratory sound envelope. The final stage of theLSD is devoted to output gain scaling and the suppression of DC baselineoffsets. These offsets can arise from a variety of sources includingcontinuous environmental sounds, rectified RFI/EMI and temperature driftin the log amplifier. The suppression of DC offsets is performedadaptively by a negative feedback loop. Negative feedback correction isproduced by averaging the LSD signal output with a long time-constantintegrator, followed by differential summation of the error with theoriginal signal. A resistance multiplying integrator achieves a timeconstant of approximately fifty-five seconds using capacitors smallerthan 1 uF.” (Eder, 1992)

The Computer (not shown in FIG. 3 ) processes the exported Signals.Those skilled in the art will understand this method to extract specificAudio Signals from a multiplicity of Audio Signals.

Referring again to FIG. 3C. The Signals that are derived by thePlethysmographic Sensor 301 and the Microphone 304 are Measured by theComputer (not shown in FIG. 3 ). Each Signal is Measured for three (3)discrete Parameters. The Measurement quantity is assigned a numericvalue that represents a direct inferential reading of the specificSignal Parameter. The Parameters that are Measured are the: Amplitude313 of the Signal. The Amplitude 313 is representative of the expansionof the Thorax or Abdomen during an inspiration. Duration of the Signal314. The Duration of the Signal 314 is the amount time that it takes foran discrete inspiration and exhalation to be completed.

Periodicity of the Signal 315. The Periodicity of the Signal 315 is thetime between discrete exhalations.

FIG. 4 is a Block diagram of the Electronic and Electrical elements ofthe invention.

The operation of the invention is illustrated in FIG. 4 . It is made upof a number of electronic component sections:

PIC Computer 409 is the Computer of the invention.

On/Off Switch 401 activates and deactivates the invention.

Control1 Switch 402 activation is the method wherein that patientinteracts with the invention.

Status LED2 403 is a multicolor LED. The color that it presents to thepatient indicates the status of the invention.

Status LED1 404 is a multicolor LED. The color that it presents to thepatient indicates the status of the invention. Battery

Pack 405 provides electrical power to the invention.

FLASH RAM 406 contains the Force Portraits 601, the Fuzzy Control SystemRules, and the Processing program instructions. The Computer 409 and itexchange data over a signal buss. SRAM 407 contains the results ofarithmetic computations by the Computer 409. The Computer 409 and itexchange data over a signal buss. Clock Oscillator 408 is the Inventionsclock. BlueTooth 410 is the section that receives Audio PortraitSignals, Alarm Signals, and Training Period 1 & 2 spoken commands,converts the signals into Bluetooth formatted Signals and wirelesslytransmits the Audio Portrait Signals to a Bluetooth wireless Earbud 715(not shown if FIG. 4 ) worn by the patient. Speaker 411 Audio PortraitSignals, Alarm Signals, and Training Period 1 & 2 spoken commands andbroadcasts them to the patient.

USB I/O Port 413 is the means by which external devices communicate withthe Computer 409. Signals 414, 415, and 416 are the busses by which theSignals are received by the Computer 409 for Processing.

FIG. 5 is a Block Diagram of the Training and Monitoring Processes.

It is a primary object of the present invention to provide a apparatusand method for detecting and terminating an Sleep Apnea event andHypopnea episode, within seconds of aid detection. To perform theprocess I draw your attention to FIG. 5A. FIG. 5A is a block diagram ofthe Process of Training. The Signals that are generated during TrainingPeriods #1 and #2 are used by the invention to perform Self-checking.This Self-checking procedure verifies that the invention is operating asintended.

The Process of Self-Checking commences when the patient dons theinvention and presses button On/Off Switch 401 (not shown in FIG. 5 ).The patient is directed to adjust the Belt 165 (not shown in FIG. 5 )and Velcro clasp by plain, spoken commands. These spoken commands arefetched from FLASH RAM 406 (not shown in FIG. 5 ) by the Computer 409(not shown in FIG. 5 ) and broadcast to the patient by Bluetoothwireless 410 (not shown in FIG. 5 ) to the patients Bluetooth Earbud 715(not shown in FIG. 5 ) and/or the Speaker 411 (not shown in FIG. 5 ).The directions are supplied to the patient to insure that the IntegratedPlethysmographics' Shuttle 270 (not shown in FIG. 5 ) is in its' restposition within Guide 275 (not shown in FIG. 5 ) that allows foruninterrupted movement of the Shuttle 270 (not shown in FIG. 5 ) duringinspiration and exhalation.

Furthermore, the Signals are Measured to become a set of ReferentialParameters (the process that is used to create these ReferentialParameters is addressed in detail later in this document).

The Process of Training: During Training Period #1, the patent isdirected to breath in specific patterns by plain, spoken commands. Thesespoken commands are fetched from FLASH RAM 406 (not shown in FIG. 5 ) bythe Computer 409 (not showing FIG. 5 ) and broadcast to the patient byBluetooth wireless 410 (not shown in FIG. 5 ) to the patients BluetoothEarbud 715 (not shown in FIG. 5 ) and/or the Speaker 411 (not shown inFIG. 5 ). This Process of Training commences when the patient dons theinvention and presses button On/Off Switch 401 (not shown in FIG. 5 )The specific patterns include but not limited to:

“Natural Breathing”

“Deep Breathing”

“Fast Breathing”

“Slow Breathing”

“No Breathing”

“Shallow Breathing”

“Breath while Supine”

“Breath on the patients Left Side”

“Breath on the patients Right Side”

“Breath while Prone”

During Training Period #2 the patent is directed to push the Control1Switch 402 (not shown in FIG. 5 ) as they are preparing to go to sleep.

All Signals are Measured by the Computer 409 (not shown in FIG. 5 ) toderive Values for the Signals intrinsic Parameters. All Signals areMeasured and Processed in an identical manner.

To illustrate how Signals are Measured by the Computer 409 (not shown inFIG. 5 ) to derive Values for the Signals' intrinsic Parameters and thenProcessed we will use the Measurement of a single Parameter as anexample. Review FIG. 5A.

For this example, the Signal Parameter that will be Measured andProcessed is “Amplitude” 316 (not shown in FIG. 5 ): The “Amplitude” isrepresentative of the expansion of the Thorax or Abdomen that occursduring an inspiration:

1. Signal Input Storage 501, collects the stream of Signals 303 (notshown in FIG. 5 ), 312 (not shown in FIG. 5 ), and 313 (not shown inFIG. 5 ) for 60 seconds.

2. Within Block 502 the Signals from within Signal Input Storage 501 areMeasured. Values are Processed so that only the largest Value for anyInspiration is kept.

-   -   a. The method of this specific Processing follows this format:        -   i. IF Value(Now) is GREATER than or EQUAL to Value(Previous)            THEN assign Value(Now) to Value(Previous).        -   ii. IF Value(Now) is Less than or Equal to Value(Previous)            THEN store Value(Previous) within Value Storage 503 as it is            the largest value for this Inspiration.

3. The stored largest Values within Value Storage 503 form a set namedVS.

4. The Values set VS is arithmetically Processed in the following mannerwithin Block 504—

-   -   a. Calculate the arithmetic average of the Values in the set VS.    -   b. Subtract each Value in the set from the arithmetic average.    -   c. Square the deviation of each Value in the set from the        arithmetic average.    -   d. Calculate the arithmetic average of the Squared deviations.    -   e. Calculate the square root of the arithmetic average of the        Squared deviations.    -   f. The result is the root-mean-square deviation.

5. The arithmetic average of the Values in the set VS is stored as aReferential Parameter in the Training Period 1 and 2 ReferentialParameter Storage 505.

6. The root-mean-square deviation of the Values in the set VS is storedas a Referential Parameter in the Training Period 1 and 2

Referential Parameter Storage 505.

The Process of Monitoring: It is a primary object of the presentinvention to provide an apparatus and method for detecting andterminating a Sleep Apnea event and Hypopnea episode, within seconds ofthe detection. FIG. 5B is a block diagram of the Process of Monitoring.The Signals Input Flow 506 comprises Signals 303 (not shown in FIG. 5 ),312 (not shown in FIG. 5 ), and 313 (not shown in FIG. 5 ).

Signals Input Flow 506 is Measured and Processed by the Computer byValue Assignment 507. The Processing steps are:

1. Upon the Measurement by the Computer 409 (not shown in FIG. 5 ) aNumeric Value is assigned for each Parameter that is Measured.

2. The Numeric Value is stored in Numeric Value Storage 508.

3. Subtraction arithmetic operation 509. Parametric Numeric Value(Now)minus it's arithmetic average Referential Parameter equals Result1.

The Numeric value for a Parameter is further Processed by the Computer(not shown in FIG. 5 ) by recalling the Referential Parameters specificto the Parameter that is being Processed at this time.

The Processing consists of a series logic operation by the Computer (notshown in FIG. 5 ). The format of these series of logic operationPerformed within Evaluation 510:

1. If Result1 is equal or Greater than 0 then Do Nothing.

2. If Result1 is Less than 0 then

-   -   a. Subtract Parametric Numeric Value(Now) from each Value        contained within the Value Set of VS.    -   b. If any result of the previous operation (step 2a) is a        positive integer then:        -   I. Divide Result1 by the root-mean square deviation            Referential Parameters parameter equals Result2.        -   II. If Results2 is Less than 0 then Do Nothing        -   III. If Results2 is Greater than 0 then present Results2 to            the Fuzzy Control System for determination as to whether            Stimulation should be applied.

FIG. 6 is a Block Diagram of the Fuzzy Control System The Detecting andTerminating Process utilizes Fuzzy logic processes. The Fuzzy ControlSystem controls two Processes.

1. Monitoring

2. Stimulation

Fuzzy logic processing is described, for example, in U.S. Pat. No.7,426,435, issued to GAUTHIER, et al. Sep. 16, 2008, The disclosures ofthese United States patents are incorporated herein by reference.Another example is NAZERAN, HOMER et al. A Fuzzy Inference System forDetection of Obstructive Sleep Apnea: Proceedings—23rd AnnualConference—IEEE/EMBS Oct. 25-28, 2001, Istanbul, TURKEY, which is herebyincorporated by reference.

Referring to FIG. 6 , the Fuzzy Control System Process for Monitoring isas follows:

Result2 values are the input variables to the Fuzzy Control System. TheResult2 values are mapped into by sets of membership functions known as“fuzzy sets”. The process of converting a Result2 values (in thenomenclature of Fuzzy Logic these Result2 values are referred to asCrisp Input Values) to a fuzzy value is called “fuzzifi-cation”. Thefuzzification” occurs in the Input stage 601 of the Fuzzy ControlSystem. The “fuzzified” Result2 values are evaluated in the next stageof the Fuzzy Control System, the Processing stage 602. The Processingstage 602 uses a collection of logic rules. The Computer then makesdecisions for what action to take based on that collection of logicrules. The Rules are in the form of IF statements:

An example of a logic rule would be:

-   -   IF amplitude IS very low AND periodicity IS very long apply        stimulation.

In this example, the two input variables are “very low” and “very long”that have values defined as fuzzy sets. The output variable,“stimulation”, is also defined by a fuzzy set that can have values like“long”, “louder, “less loud”, and so on.

The results of the Processing Stage are combined to give a specific(“Crisp”) answer; this “Crisp” answer translates results into values.This takes place in the Crisp Control Stage 604. If the “Crisp” answeris to initiate Stimulation then the Process steps are as described orshown herein.

FIG. 7 is a diagram of a typical Patient wearing the invention. Patient700, has the positioned the Housing 705 on his Thorax and has fastenedBelt 710 to hold it in place. The patient 700 is wearing the BluetoothEarbud 715.

FIG. 8 is a Block Diagram of Portrait Development.

Before continuing it may be advantageous to set forth definitions ofcertain words and phrases.

Stored Portrait Stimulation Parameters are:

-   -   Effective Portraits    -   Irritation Index    -   Audio Portrait    -   Force Portrait    -   Effectivity Index        Effective Portraits:

Is that combination of an Audio Portrait and a Force Portrait that havebeen found through a Process (described below) to generate aninspiration in a Patient who is having an Sleep Apnea event or Hypopneaepisode.

Irritation Index:

The Irritation Index is an arbitrary value assigned to Portraits Audioand Force at the time that the Portrait is created and inputted into theFLASH RAM 406. It is indicative of how reactive a patient would be tothat Portrait, As an example, the playing of an Audio file of a womanscreaming would be assigned a higher Irritation Index value than that ofAudio file of a birds singing.

Force Portrait:

The mechanical tactile sensory stimulator 200 (not shown in FIG. 6 )differ from a simple vibrator in that it is capable of simulating a widerange of tactile effects. The Haptic effects are assembled by usingsoftware instructions to control the force amplitude, wave shape, andpulse duration to the stimulation effectors. These instructions arecombined to form Force Portraits. The Force Portraits are stored in theHaptic effects library area of the Portrait Storage 801 (not shown inFIG. 6 ). Different Force Portraits are felt as different tactilesensations by the patients. These Force Portraits are assigned anIrritation Index value. The choice of which Force Portrait to use forthe mechanical tactile sensory stimulator is determined by the FuzzyLogic System.

Audio Portrait

A method of Stimulation is the playing of prerecorded Audio files. TheseAudio files are stored in the Portrait Storage 801 (not shown in FIG. 6) as Audio Portraits. The Audio Portrait is made up the Audio File Name,a Volume value, the File length, and the Audio File Irritation Indexvalue. There are multiplicities of stored Audio Portrait. The Audiofiles are sent to the patient by a Bluetooth wireless transmitter 410(not shown in FIG. 6 ) to a Bluetooth wireless Earbud 715 (not shown inFIG. 6 ). Bluetooth is a wireless protocol utilizing short-rangecommunications technology facilitating data transmission over shortdistances from fixed and/or mobile device. Bluetooth wirelesscommunication is described, for example, in U.S. Pat. No. 7,225,064,issued to FUDALI, et al. May 29, 2007. The disclosures of these UnitedStates patents are incorporated herein by reference. The choice of whichAudio Portrait to use for the Audio Stimulus is determined by the FuzzyLogic System.

Effectivity Index:

The Effectivity Index is the sum of the Irritation Indexes of an Audioand Force Portraits couple. The larger the numerical value of theEffectivity Index than the more vigorous the Stimulus delivered to thepatient. The present invention relates to an apparatus to detect and endan occurrence of a Sleep Apnea event or Hypopnea episode, in a mannerthat will decrease or eliminate hypoxia, hypercapnia and the disturbanceof pulmonary hemodynamics.

To apply Stimulus in a manner that will decrease or eliminate hypoxia,hypercapnia and the disturbance of pulmonary hemodynamics it isnecessary to determine what stimuli is both effective in initiatingInspiration within 2 seconds of the stimulus application whilesimultaneously decreasing or eliminating the disturbance of pulmonaryhemodynamics.

The Method to develop a set of stimuli that is both effective ininitiating Inspiration within 2 seconds of the Stimulus applicationwhile simultaneously decreasing or eliminating the disturbance ofpulmonary hemodynamics is as follows. The sets of stimuli are calledEffective Portraits.

When the Fuzzy Control System Process of FIG. 6 (not shown in FIG. 8 )detects the onset of a Sleep Apnea event or Hypopnea episode, itattempts to select the of Effective Portrait from within PortraitStorage 801.

If there is no Effective Portrait as would happen when the patientinitially dons the invention then the Process of developing an EffectivePortrait commences:

1. The Fuzzy Control System of FIG. 6 (not shown in FIG. 8 ) inputs arandom selection of a Force and Audio Portrait from the Portrait Library802 forming a Temporary Couple.

2. The Temporary Couple is sent to the Stimulus Effectors 806.

3. After a 2 Second Delay 805 the Fuzzy Logic System of FIG. 6 (notshown in FIG. 8 ) Monitors the patient to determine if there is aninspiration.

4. If Fuzzy Logic System of FIG. 6 (not shown in FIG. 8 ) determinesthat further Stimulation is required then another random selection of aForce and Audio Portrait is made from the Portrait Library 802 forminganother Temporary Couple.

5. This Temporary Couple will have a larger Effectivity Index than theprevious Temporary Couple Effectivity Index.

6. This Temporary Couple is sent to the Stimulus Effectors 806.

7. After a 2 Second Delay 805 the Fuzzy Logic System of FIG. 6 (notshown in FIG. 8 ) Monitors the patient to determine if there is aninspiration.

8. Steps 5-7 cycle until the Fuzzy Logic System of FIG. 6 (not shown inFIG. 8 ) determines that Stimulus is no longer required. The TemporaryCouple is stored in Portrait Storage 801 as an Effective Portrait.

Effectivity of the Effective Portrait changes in a cyclic pattern duringsleep as the amount of Stimulus required to initiate an inhalation waxesand wanes.

This is the Method for adapting to that cyclic process—

When the Fuzzy Control System Process of FIG. 6 (not shown in FIG. 8 )detects the onset of a Sleep Apnea event or Hypopnea episode, itattempts to use the Effective Portrait that has been stored in PortraitStorage 801.

If there is an Effective Portrait in Portrait Storage 801 then the FuzzyControl System of FIG. 6 (not shown in FIG. 8 ) will:

1. Send that Effective Portrait to the Stimulus Effectors 806.

2. After a 2 Second Delay 805 the Fuzzy Logic System of FIG. 6 (notshown in FIG. 8 ) Monitors the patient. If the Fuzzy Logic System ofFIG. 6 (not shown in FIG. 8 ) determines that further Stimulation isrequired—.

-   -   a Force and Audio Portrait is chosen from the Portrait Library        802 forming a Temporary Couple whose Effectivity Index is        incrementally greater than the Effectivity Index of the        Effective Portrait stored in Portrait Storage 801.    -   b. Sends that Effective Portrait to the Stimulus Effectors 806.        -   i. Step 2 cycles until the Fuzzy Logic System of FIG. 6 (not            shown if FIG. 8 ) determines that there exists' no need            further for Stimulation (an inhalation is detected).        -   ii. This Temporary Couple replaces the Effective Portrait            stored within Portrait Storage 801.

3. If the Fuzzy Logic System of FIG. 6 (not shown in FIG. 8 ) determinesthat no further Stimulation is required then when the next Sleep Apneaevent or Hypopnea episode is detected—.

-   -   a Force and Audio Portrait is chosen from the Portrait Library        802 forming a Temporary Couple whose Effectivity Index is        incrementally less than the Effectivity Index of the Effective        Portrait stored in Portrait Storage 801.    -   b. Sends that Temporary Couple to the Stimulus Effectors 806.    -   c. After a 2 Second Delay 805 the Fuzzy Logic System of FIG. 6        (not shown in FIG. 8 ) Monitors the patient.        -   i. If the Fuzzy Logic System of FIG. 6 (not shown in FIG. 8            ) determines that no further Stimulation is required then            this Temporary Couple replaces the Effective Portrait stored            within Portrait Storage 801.        -   ii. If the Fuzzy Logic System of FIG. 6 (not shown in FIG. 8            ) determines further Stimulation is required then 1) A Force            and Audio Portrait is chosen from the Portrait Library 802            forming a Temporary Couple whose Effectivity Index is            incrementally greater than the Effectivity Index of the            Effective Portrait stored in Portrait Storage 801.

2) Sends that Effective Portrait to the Stimulus Effectors 806.

3) After a 2 Second Delay 805 the Fuzzy Logic System of FIG. 6 (notshown in FIG. 8 ) Monitors the patient.

4) Step 3) cycles until the Fuzzy Logic System of FIG. 6 (not shown ifFIG. 8 ) determines that there exists' no need further for Stimulation(an inhalation is detected.

5) This Temporary Couple replaces the Effective Portrait stored withinPortrait Storage 801.

CITATION LIST Patent Literature

U.S. Pat. No. 7,387,608 Apparatus and method for the treatment of sleeprelated disorders Jun. 1, 2008 Dunlop; David A, Gunderman, Jr.; RobertDale

-   -   U.S. Pat. No. 7,371,220 System and method for real-time        apnea/hypopnea detection using an implantable medical system May        1, 2008 Koh; Steve, Park; Euljoon, Benser    -   2005/0085865 Breathing disorder detection and therapy delivery        device and method Apr. 1, 2005 Tehrani, Amir J    -   2006/0097879 SIDS and apnea monitoring system May 1, 2006        Lippincott; Kathy J    -   2005/0101833 Apparatus for the treatment of sleep apnea May 1,        2005 Hsu, William    -   U.S. Pat. No. 6,935,335 System and method for treating        obstructive sleep apnea Aug. 1, 2005 Lehrman; Michael L.,        Halleck; Michael E    -   U.S. Pat. No. 6,666,830 System and method for detecting the        onset of an obstructive sleep apnea event Dec. 1, 2003 Lehrman;        Michael L., Halleck; Michael E. Ferguson; Pete, Kumar; Harpal,        Lay; Graham, Llewellyn; Mike, Place; John D.    -   U.S. Pat. No. 6,241,683 Phonospirometry for non-invasive        monitoring of respiration Jun. 1, 2001 Macklem; Peter T., Que;        Cheng-Li, Kelly; Suzanne M., Kolmaga; Krzystof, Durand;        Louis-Gilles    -   U.S. Pat. No. 6,290,654 Obstructive sleep apnea detection        apparatus and method using pattern recognition Sep. 1, 2001        Karakasoglu; Ahmet    -   U.S. Pat. No. 6,011,477 Respiration and movement monitoring        system Jan. 4, 2000 Teodorescu; Horia-Nicolai, Mlynek; Daniel J.    -   U.S. Pat. No. 5,853,005 Acoustic monitoring system Dec. 1, 1998        Scanlon; Michael V    -   U.S. Pat. No. 5,769,084 Method and apparatus for diagnosing        sleep breathing disorders Jun. 1, 1998 Katz; Richard A., Lawee;        Michael S., Newman; A. Kief    -   U.S. Pat. No. 5,555,891 Vibrotactile stimulator system for        detecting and interrupting apnea in infants Sep. 1, 1996        Eisenfeld; Leonard I.    -   U.S. Pat. No. 5,540,733 Method and apparatus for detecting and        treating obstructive sleep apnea Jul. 1, 1996 Testerman; Roy L.,        Erickson; Donald J., Bierbaum; Ralph W.    -   U.S. Pat. No. 5,522,862 Method and apparatus for treating        obstructive sleep apnea Jun. 4, 1996, Testerman; Roy L.,        Erickson; Donald J.    -   U.S. Pat. No. 5,277,194 Breathing monitor and stimulator, Jan.        11, 1994. Hosterman; Craig, Smith; Alvin W.    -   U.S. Pat. No. 5,107,855 Apena monitor for detection of aperiodic        sinusoidal movement Apr. 1, 1992 Harrington; Reginald, Crossley;        Ralph    -   U.S. Pat. No. 5,050,614 Apparatus and method for inspiration        detection Sep. 1, 1991 Logan; Charles H.    -   U.S. Pat. No. 4,781,201 Cardiovascular artifact filter Nov. 1,        1988 Wright; John C., Triebel    -   U.S. Pat. No. 4,694,839 Auxiliary stimulation apparatus for        apnea distress Sep. 1, 1987 Timme; William F.    -   U.S. Pat. No. 4,686,999 Multi-channel ventilation monitor and        method Aug. 1, 1987 Snyder; Leon T., Scarfone; Frank A., Reuss;        James L., Campen; George V., Yates; George H.    -   U.S. Pat. No. 4,365,636 Method of monitoring patient respiration        and predicting apnea there from Dec. 1, 1982 Barker; Kent R.    -   U.S. Pat. No. 4,296,757 Respiratory monitor and excessive        intrathoracic or abdominal pressure indicator Oct. 1, 1981        Taylor; Thomas    -   CONTINUATION APPLICATION 2505240 OSA HYPOXIA ONSET DETECTOR AND        INTERRUPTOR Nov. 26, 2007

Non-Patent Literature

-   H. SCHNEIDER et al, “Effects of arousal and sleep state on systemic    and pulmonary hemodynamics in obstructive apnea”, J. Appl. Physiol.    88: 1084-1092, 2000.-   D. M. Carlson et al, “Acoustically induced cortical arousal    increases phasic pharyngeal muscle and diaphragmatic EMG in NREM    sleep”, Journal of Applied Physiology, Vol 76, Issue 4 1553-1559.-   W. T. McNicholas, “Arousal in the sleep apnea syndrome: a mixed    blessing?”, Eur Respir J 1998; 12: 1239-1241.-   Robert C. Basner M D et al, “Respiratory and Arousal Responses to    Acoustic Stimulation”, Chest. 1997; 112:1567-1571.-   Gang Bao et al., “Acute and chronic blood pressure response to    recurrent acoustic arousal in rats”, Am J Hypertens (1999) 12,    504-510.-   R. C. Basner et al, “Effect of induced transient arousal on    obstructive apnea duration”, J. App Physiol. 78(4): 1469-1476, 1995.-   Dina Brooks et al, “Obstructive Sleep Apnea as a Cause of Systemic    Hypertension Evidence from a Canine Model”, J. Clin. Invest. Volume    99, Number 1, January 1997, 106-109.-   MARY J. MORRELL et al, “Sleep Fragmentation, Awake Blood Pressure,    and Sleep-Disordered Breathing in a Population-based Study”, Am. J.    Respir. Crit. Care Med., Volume 162, Number 6, December 2000,    2091-2096.-   Robert C. Basner et al, “Respiratory and Arousal Responses to    Acoustic Stimulation”, Chest 1997; 112; 1567-1571.-   RICHARD S. T. LEUNG et al, “Sleep Apnea and Cardiovascular Disease”,    Am. J. Respir. Crit. Care Med., Volume 164, Number 12, December    2001, 2147-2165.-   Denise M. O'Driscoll et al, “Cardiovascular response to arousal from    sleep under controlled conditions of central and peripheral    chemoreceptor stimulation in humans”, J Appl Physiol 96:865-870,    2004.-   Denise M. O'Driscoll et al, “Occlusion of the upper airway does not    augment the cardiovascular response to arousal from sleep in    humans”, J Appl Physiol 98:1349-1355, 2005.-   U. Leuenberger et al, “Surges of muscle sympathetic nerve activity    during obstructive apnea are linked to hypoxemia”, Am. J. Respir.    Crit. Care Med., Volume 164, Number 12, December 2001, 2147-2165.-   RICHARD S. T. LEUNG et al, “Sleep Apnea and Cardiovascular Disease”,    Journal of Applied Physiology, Vol 79, Issue 2 581-588.-   Richard B. Berry M D, “Sleep Apnea Impairs the Arousal Response to    Airway Occlusion”, Chest. 1996; 109:1490-1496.-   T. KATO et al, “Experimentally induced arousals during sleep: a    cross-modality matching paradigm”, J. Sleep Res. (2004) 13, 229-23.-   Christian Guilleminault et al, “The effect of CNS activation versus    EEG arousal during sleep on heart rate response and daytime tests”,    Clinical Neurophysiology 117 (2006) 731-739.-   Emilia Sforza, M D et al, “Effects of Sleep Deprivation on    Spontaneous Arousals in Humans”, SLEEP, Vol. 27, No. 6, 2004.-   J. F. Masa et al, “Assessment of thoracoabdominal bands to detect    respiratory effort-related arousal”, Eur Respir J 2003; 22: 661-667.-   R. C. Basner et al, “Effect of induced transient arousal on    obstructive apnea duration”, J Appl Physiol 78: 1469-1476, 1995.-   HIROSHI MIKI et al, “New Treatment for Obstructive Apnea Syndrome by    Electrical Stimulation of Submental Region”, Tohoku J. exp. Med.,    1988, 154, 91-92.-   C. Guilleminault et al, “The effect of CNS activation versus EEG    arousal during sleep on heart rate response and daytime tests”,    Clinical Neurophysiology, Volume 117, Issue 4, Pages 731-739.-   Immersion Corporation, “Next-generation TouchSense Vibration for    Video Game Console Systems”, 31 Aug. 2006.-   Sheroz Khan, I. Adam et al, “Rule-Based Fuzzy Logic Controller with    Adaptable Reference”, International Journal of Intelligent    Technology Volume 3 Number 1.-   E. Sforza et al, “Nocturnal evolution of respiratory effort in    obstructive sleep apnoea syndrome: influence on arousal threshold,    Eur Respir J 1998; 121257-126 DOI: 10.1183/09031936.98.12061257.-   Homer Nazeran et al, “A Fuzzy Inference System for Detection of    Obstructive Sleep Apnea”. Proceedings—23rd Annual    Conference—IEEE/EMBS Oct. 25-28, 2001, Istanbul, TURKEY.

What is claimed is:
 1. A system for treating a breathing disordercomprising: a sensor capable of detecting physiologic signals; a patientstimulator configured to operate independently of any administration ofgases or positive airway pressure; a processor connected to the sensorand the patient stimulator, the processor being configured to processinformation from the sensor to detect patterns and abnormalities ofrespiration of a patient, and to determine a physiologic state of thepatient; select, in response to the physiologic state of the patient,from a group of stimuli consisting of stationary auditory stimuli andnon-stationary auditory stimuli having time-varying frequency content, afirst stimulus comprising a stationary auditory stimulus and a secondstimulus comprising a non-stationary auditory stimulus havingtime-varying frequency content; configure, in response to thephysiologic state of the patient, attributes of each selected stimulusto elicit a desired physiologic response comprising initiation ofinhalation while avoiding or mitigating an undesired physiologicresponse comprising recruitment of the ascending arousal system andtransition from a deeper stage of sleep to a lighter stage of sleep, theattributes including a start timing, an intensity, and a duration; andgenerate a control signal to cause the stimulator to deliver eachselected stimulus in response to detecting a physiologic state thatpredicts an onset of an apnea or a hypopnea, and to terminate deliveryof stimuli immediately upon detection of an inhalation, so that stimuliare not delivered when the patient is breathing normally; wherein thesystem is configured to operate without any requirement for anyintervention by a health professional and without any requirement fordetermination of baseline parameters performed outside of the system orentry of baseline parameters into the system.
 2. The system of claim 1,the processor being further configured to generate a control signal tocause the stimulator to deliver each selected stimulus at a start timesynchronized to a physiologic signal detected by the sensor.
 3. Thesystem of claim 1, wherein the processor is further configured togenerate a control signal to cause the stimulator to deliver eachselected stimulus to elicit initiation of inhalation before airflow hasbeen interrupted for a full 10 seconds, so that the interruption ofairflow is less than 10 seconds.
 4. The system of claim 1, wherein theprocessor is further configured to configure the modifiable attributesand timing of each selected stimulus to prevent habituation.
 5. Thesystem of claim 1, wherein the processor is further configured toconfigure the attributes of each selected stimulus to avoid or mitigatean additional undesired physiologic response selected from the groupconsisting of altered cardiac activity, increased systolic bloodpressure, and increased circulating catecholamines.
 6. The system ofclaim 1, wherein the sensor comprises a microphone.
 7. The system ofclaim 1, wherein the sensor comprises a plethysmograph.
 8. The system ofclaim 1, wherein the sensor comprises a photodetector.
 9. The system ofclaim 1, wherein the non-stationary auditory stimuli having time-varyingfrequency content comprise naturalistic audio signals.
 10. The system ofclaim 1 wherein the processor is further configured to select, inresponse to the physiologic state of the patient, an additional stimulusfrom a group of stimuli consisting of haptic stimuli.
 11. The system ofclaim 1 wherein the processor is further configured to select, inresponse to the physiologic state of the patient, an additional stimulusfrom a group of stimuli consisting of optical stimuli.
 12. A method fortreating a breathing disorder comprising: processing information from asensor capable of detecting physiologic signals to detect patterns andabnormalities of respiration of a patient, and to determine aphysiologic state of the patient; selecting, in response to thephysiologic state of the patient, from a group of stimuli consisting ofstationary auditory stimuli and non-stationary auditory stimuli havingtime-varying frequency content, a first stimulus comprising a stationaryauditory stimulus and a second stimulus comprising a non-stationaryauditory stimulus having time-varying frequency content; configuring, inresponse to the physiologic state of the patient, attributes of eachselected stimulus to elicit a desired physiologic response comprisinginitiation of inhalation while avoiding or mitigating an undesiredphysiologic response comprising recruitment of the ascending arousalsystem and transition from a deeper stage of sleep to a lighter stage ofsleep, the attributes including a start timing, an intensity, and aduration; delivering, independent of any administration of gases orpositive airway pressure, each selected stimulus to the patient usingthe patient stimulator in response to detecting a physiologic state thatpredicts an onset of an apnea or a hypopnea, and terminating delivery ofstimuli immediately upon detection of inhalation, so that stimuli arenot delivered when the patient is breathing normally; and operatingwithout any requirement for any intervention by a health professionaland without any requirement for determination of baseline parametersperformed outside of the system or entry of baseline parameters into thesystem.
 13. The method of claim 12, wherein each selected stimulus isdelivered at a time synchronized to a physiologic signal detected by thesensor.
 14. The method of claim 12, wherein a physiologic state isdetected that predicts onset of an apnea or hypopnea and each selectedstimulus is delivered to elicit initiation of inhalation before airflowhas been interrupted for a full 10 seconds, so that the interruption ofairflow is less than 10 seconds.
 15. The method of claim 12, wherein theattributes and timing of each selected stimulus are chosen to preventhabituation.
 16. The method of claim 12, wherein the steps of the methodare performed while the patient is using a Positive Airway Pressuremachine.
 17. The method of claim 12, wherein the attributes of eachselected stimulus are further configured to avoid an additionalundesired physiologic response selected from the group consisting ofaltered cardiac activity, increased systolic blood pressure, andincreased circulating catecholamines.
 18. The method of claim 12,wherein the sensor comprises a microphone.
 19. The method of claim 12,wherein an additional stimulus is selected, in response to thephysiologic state of the patient, from a group of stimuli consisting ofhaptic stimuli.
 20. The method of claim 12, wherein an additionalstimulus is selected, in response to the physiologic state of thepatient, from a group of stimuli consisting of optical stimuli.